Journal articles on the topic 'Latency'
To see the other types of publications on this topic, follow the link: Latency.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Latency.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Rezaei, Simin D., Hao K. Lu, J. Judy Chang, Ajantha Rhodes, Sharon R. Lewin, and Paul U. Cameron. "The Pathway To Establishing HIV Latency Is Critical to How Latency Is Maintained and Reversed." Journal of Virology 92, no. 13 (April 11, 2018): e02225-17. http://dx.doi.org/10.1128/jvi.02225-17.
Full textAbstract:
ABSTRACTHIV infection requires lifelong antiretroviral therapy because of the persistence of latently infected CD4+T cells. The induction of virus expression from latently infected cells occurs following T cell receptor (TCR) activation, but not all latently infected cells respond to TCR stimulation. We compared two models of latently infected cells using an enhanced green fluorescent protein (EGFP) reporter virus to infect CCL19-treated resting CD4+(rCD4+) T cells (preactivation latency) or activated CD4+T cells that returned to a resting state (postactivation latency). We isolated latently infected cells by sorting for EGFP-negative (EGFP−) cells after infection. These cells were cultured with antivirals and stimulated with anti-CD3/anti-CD28, mitogens, and latency-reversing agents (LRAs) and cocultured with monocytes and anti-CD3. Spontaneous EGFP expression was more frequent in postactivation than in preactivation latency. Stimulation of latently infected cells with monocytes/anti-CD3 resulted in an increase in EGFP expression compared to that for unstimulated controls using the preactivation latency model but led to a reduction in EGFP expression in the postactivation latency model. The reduced EGFP expression was not associated with reductions in the levels of viral DNA or T cell proliferation but depended on direct contact between monocytes and T cells. Monocytes added to the postactivation latency model during the establishment of latency reduced spontaneous virus expression, suggesting that monocyte-T cell interactions at an early time point postinfection can maintain HIV latency. This direct comparison of pre- and postactivation latency suggests that effective strategies needed to reverse latency will depend on how latency is established.IMPORTANCEOne strategy being evaluated to eliminate latently infected cells that persist in HIV-infected individuals on antiretroviral therapy (ART) is to activate HIV expression or production with the goal of inducing virus-mediated cytolysis or immune-mediated clearance of infected cells. The gold standard for the activation of latent virus is T cell receptor stimulation with anti-CD3/anti-CD28. However, this stimulus activates only a small proportion of latently infected cells. We show clear differences in the responses of latently infected cells to activating stimuli based on how latent infection is established, an observation that may potentially explain the persistence of noninduced intact proviruses in HIV-infected individuals on ART.
2
Virgin, Herbert W., Rachel M. Presti, Xi-Yang Li, Carl Liu, and Samuel H. Speck. "Three Distinct Regions of the Murine Gammaherpesvirus 68 Genome Are Transcriptionally Active in Latently Infected Mice." Journal of Virology 73, no. 3 (March 1, 1999): 2321–32. http://dx.doi.org/10.1128/jvi.73.3.2321-2332.1999.
Full textAbstract:
ABSTRACT The program(s) of gene expression operating during murine gammaherpesvirus 68 (γHV68) latency is undefined, as is the relationship between γHV68 latency and latency of primate gammaherpesviruses. We used a nested reverse transcriptase PCR strategy (sensitive to approximately one copy of γHV68 genome for each genomic region tested) to screen for the presence of viral transcripts in latently infected mice. Based on the positions of known latency-associated genes in other gammaherpesviruses, we screened for the presence of transcripts corresponding to 11 open reading frames (ORFs) in the γHV68 genome in RNA from spleens and peritoneal cells of latently infected B-cell-deficient (MuMT) mice which have been shown contain high levels of reactivable latent γHV68 (K. E. Weck, M. L. Barkon, L. I. Yoo, S. H. Speck, and H. W. Virgin, J. Virol. 70:6775–6780, 1996). To control for the possible presence of viral lytic activity, we determined that RNA from latently infected peritoneal and spleen cells contained few or no detectable transcripts corresponding to seven ORFs known to encode viral gene products associated with lytic replication. However, we did detect low-level expression of transcripts arising from the region of gene 50 (encoding the putative homolog of the Epstein-Barr virus BRLF1 transactivator) in peritoneal but not spleen cells. Latently infected peritoneal cells consistently scored for expression of RNA derived from 4 of the 11 candidate latency-associated ORFs examined, including the regions of ORF M2, ORF M11 (encoding v-bcl-2), gene 73 (a homolog of the Kaposi’s sarcoma-associated herpesvirus [human herpesvirus 8] gene encoding latency-associated nuclear antigen), and gene 74 (encoding a G-protein coupled receptor homolog, v-GCR). Latently infected spleen cells consistently scored positive for RNA derived from 3 of the 11 candidate latency-associated ORFs examined, including ORF M2, ORF M3, and ORF M9. To further characterize transcription of these candidate latency-associated ORFs, we examined their transcription in lytically infected fibroblasts by Northern analysis. We detected abundant transcription from regions of the genome containing ORF M3 and ORF M9, as well as the known lytic-cycle genes. However, transcription of ORF M2, ORF M11, gene 73, and gene 74 was barely detectable in lytically infected fibroblasts, consistent with a role of these viral genes during latent infection. We conclude that (i) we have identified several candidate latency genes of murine γHV68, (ii) expression of genes during latency may be different in different organs, consistent with multiple latency programs and/or multiple cellular sites of latency, and (iii) regions of the viral genome (v-bcl-2 gene, v-GCR gene, and gene 73) are transcribed during latency with both γHV68 and primate gammaherpesviruses. The implications of these findings for replacing previous operational definitions of γHV68 latency with a molecular definition are discussed.
3
Jefferys, Stuart R., Samuel D. Burgos, Jackson J. Peterson, Sara R. Selitsky, Anne-Marie W. Turner, Lindsey I. James, Yi-Hsuan Tsai, et al. "Epigenomic characterization of latent HIV infection identifies latency regulating transcription factors." PLOS Pathogens 17, no. 2 (February 26, 2021): e1009346. http://dx.doi.org/10.1371/journal.ppat.1009346.
Full textAbstract:
Transcriptional silencing of HIV in CD4 T cells generates a reservoir of latently infected cells that can reseed infection after interruption of therapy. As such, these cells represent the principal barrier to curing HIV infection, but little is known about their characteristics. To further our understanding of the molecular mechanisms of latency, we characterized a primary cell model of HIV latency in which infected cells adopt heterogeneous transcriptional fates. In this model, we observed that latency is a stable, heritable state that is transmitted through cell division. Using Assay of Transposon-Accessible Chromatin sequencing (ATACseq) we found that latently infected cells exhibit greatly reduced proviral accessibility, indicating the presence of chromatin-based structural barriers to viral gene expression. By quantifying the activity of host cell transcription factors, we observe elevated activity of Forkhead and Kruppel-like factor transcription factors (TFs), and reduced activity of AP-1, RUNX and GATA TFs in latently infected cells. Interestingly, latency reversing agents with different mechanisms of action caused distinct patterns of chromatin reopening across the provirus. We observe that binding sites for the chromatin insulator CTCF are highly enriched in the differentially open chromatin of infected CD4 T cells. Furthermore, depletion of CTCF inhibited HIV latency, identifying this factor as playing a key role in the initiation or enforcement of latency. These data indicate that HIV latency develops preferentially in cells with a distinct pattern of TF activity that promotes a closed proviral structure and inhibits viral gene expression. Furthermore, these findings identify CTCF as a novel regulator of HIV latency.
4
Maillet, Séverine, Thierry Naas, Sophie Crepin, Anne-Marie Roque-Afonso, Florence Lafay, Stacey Efstathiou, and Marc Labetoulle. "Herpes Simplex Virus Type 1 Latently Infected Neurons Differentially Express Latency-Associated and ICP0 Transcripts." Journal of Virology 80, no. 18 (September 15, 2006): 9310–21. http://dx.doi.org/10.1128/jvi.02615-05.
Full textAbstract:
ABSTRACT During the latent phase of herpes simplex virus type 1 (HSV-1) infection, the latency-associated transcripts (LATs) are the most abundant viral transcripts present in neurons, but some immediate-early viral transcripts, such as those encoding ICP0, have also been reported to be transcribed in latently infected mouse trigeminal ganglia (TG). A murine oro-ocular model of herpetic infection was used to study ICP0 gene expression in the major anatomical sites of HSV-1 latency, including the TG, superior cervical ganglion, spinal cord, and hypothalamus. An HSV-1 recombinant strain, SC16 110LacZ, revealed ICP0 promoter activity in several neurons in latently infected ganglia, and following infection with wild-type HSV-1 strain SC16, in situ hybridization analyses identified ICP0 transcripts in the nuclei of neurons at times consistent with the establishment of latency. Reverse transcription (RT)-PCR assays performed on RNA extracted from latently infected tissues indicated that ICP0 transcripts were detected in all anatomical sites of viral latency. Furthermore, quantitative real-time RT-PCR showed that neurons differentially expressed the LATs and ICP0 transcripts, with splicing of ICP0 transcripts being dependent on the anatomical location of latency. Finally, TG neurons were characterized by high-level expression of LATs and detection of abundant unspliced ICP0 transcripts, a pattern markedly different from those of other anatomical sites of HSV-1 latency. These results suggest that LATs might be involved in the maintenance of HSV-1 latency through the posttranscriptional regulation of ICP0 in order to inhibit expression of this potent activator of gene expression during latency.
5
Usherwood, Edward J., Douglas J. Roy, Kim Ward, Sherri L. Surman, Bernadette M. Dutia, Marcia A. Blackman, James P. Stewart, and David L. Woodland. "Control of Gammaherpesvirus Latency by Latent Antigen-Specific Cd8+ T Cells." Journal of Experimental Medicine 192, no. 7 (September 25, 2000): 943–52. http://dx.doi.org/10.1084/jem.192.7.943.
Full textAbstract:
The contribution of the latent antigen-specific CD8+ T cell response to the control of gammaherpesvirus latency is currently obscure. Some latent antigens induce potent T cell responses, but little is known about their induction or the role they play during the establishment of latency. Here we used the murine gammaherpesvirus system to examine the expression of the latency-associated M2 gene during latency and the induction of the CD8+ T cell response to this protein. M2, in contrast to the M3 latency-associated antigen, was expressed at day 14 after infection but was undetectable during long-term latency. The induction of the M291–99/Kd CD8+ T cell response was B cell dependent, transient, and apparently induced by the rapid increase in latently infected cells around day 14 after intranasal infection. These kinetics were consistent with a role in controlling the initial “burst” of latently infected cells. In support of this hypothesis, adoptive transfer of an M2-specific CD8+ T cell line reduced the initial load of latently infected cells, although not the long-term load. These data represent the first description of a latent antigen-specific immune response in this model, and suggest that vaccination with latent antigens such as M2 may be capable of modulating latent gammaherpesvirus infection.
6
Liu, Yilin, Morgan Hancock, Aspen Workman, Alan Doster, and Clinton Jones. "β-Catenin, a Transcription Factor Activated by Canonical Wnt Signaling, Is Expressed in Sensory Neurons of Calves Latently Infected with Bovine Herpesvirus 1." Journal of Virology 90, no. 6 (January 6, 2016): 3148–59. http://dx.doi.org/10.1128/jvi.02971-15.
Full textAbstract:
ABSTRACTLike manyAlphaherpesvirinaesubfamily members, bovine herpesvirus 1 (BoHV-1) expresses an abundant transcript in latently infected sensory neurons, the latency-related (LR)-RNA. LR-RNA encodes a protein (ORF2) that inhibits apoptosis, interacts with Notch family members, interferes with Notch-mediated transcription, and stimulates neurite formation in cells expressing Notch. An LR mutant virus containing stop codons at the amino terminus of ORF2 does not reactivate from latency or replicate efficiently in certain tissues, indicating that LR gene products are important. In this study, β-catenin, a transcription factor activated by the canonical Wnt signaling pathway, was frequently detected in ORF2-positive trigeminal ganglionic neurons of latently infected, but not mock-infected, calves. Conversely, the lytic cycle regulatory protein (BoHV-1 infected cell protein 0, or bICP0) was not frequently detected in β-catenin-positive neurons in latently infected calves. During dexamethasone-induced reactivation from latency, mRNA expression levels of two Wnt antagonists, Dickkopf-1 (DKK-1) and secreted Frizzled-related protein 2 (SFRP2), were induced in bovine trigeminal ganglia (TG), which correlated with reduced β-catenin protein expression in TG neurons 6 h after dexamethasone treatment. ORF2 and a coactivator of β-catenin, mastermind-like protein 1 (MAML1), stabilized β-catenin protein levels and stimulated β-catenin-dependent transcription in mouse neuroblastoma cells more effectively than MAML1 or ORF2 alone. Neuroblastoma cells expressing ORF2, MAML1, and β-catenin were highly resistant to cell death following serum withdrawal, whereas most cells transfected with only one of these genes died. The Wnt signaling pathway interferes with neurodegeneration but promotes neuronal differentiation, suggesting that stabilization of β-catenin expression by ORF2 promotes neuronal survival and differentiation.IMPORTANCEBovine herpesvirus 1 (BoHV-1) is an important pathogen of cattle, and like manyAlphaherpesvirinaesubfamily members establishes latency in sensory neurons. Lifelong latency and the ability to reactivate from latency are crucial for virus transmission. Maintaining the survival and normal functions of terminally differentiated neurons is also crucial for lifelong latency. Our studies revealed that BoHV-1 gene products expressed during latency stabilize expression of the transcription factor β-catenin and perhaps its cofactor, mastermind-like protein 1 (MAML1). In contrast to expression during latency, β-catenin expression in sensory neurons is not detectable following treatment of latently infected calves with the synthetic corticosteroid dexamethasone to initiate reactivation from latency. A viral protein (ORF2) expressed in a subset of latently infected neurons stabilized β-catenin and MAML1 in transfected cells. ORF2, β-catenin, and MAML1 also enhanced cell survival when growth factors were withdrawn, suggesting that these genes enhance survival of latently infected neurons.
7
Taura, Manabu, Eric Song, Ya-Chi Ho, and Akiko Iwasaki. "Apobec3A maintains HIV-1 latency through recruitment of epigenetic silencing machinery to the long terminal repeat." Proceedings of the National Academy of Sciences 116, no. 6 (January 22, 2019): 2282–89. http://dx.doi.org/10.1073/pnas.1819386116.
Full textAbstract:
HIV-1 integrates into the genome of target cells and establishes latency indefinitely. Understanding the molecular mechanism of HIV-1 latency maintenance is needed for therapeutic strategies to combat existing infection. In this study, we found an unexpected role for Apobec3A (apolipoprotein B MRNA editing enzyme catalytic subunit 3A, abbreviated “A3A”) in maintaining the latency state within HIV-1–infected cells. Overexpression of A3A in latently infected cell lines led to lower reactivation, while knockdown or knockout of A3A led to increased spontaneous and inducible HIV-1 reactivation. A3A maintains HIV-1 latency by associating with proviral DNA at the 5′ long terminal repeat region, recruiting KAP1 and HP1, and imposing repressive histone marks. We show that knockdown of A3A in latently infected human primary CD4 T cells enhanced HIV-1 reactivation. Collectively, we provide evidence and a mechanism by which A3A reinforces HIV-1 latency in infected CD4 T cells.
8
Satheesan, Sangeetha, Haitang Li, John C. Burnett, Mayumi Takahashi, Shasha Li, Shiny Xiaqin Wu, Timothy W. Synold, John J. Rossi, and Jiehua Zhou. "HIV Replication and Latency in a Humanized NSG Mouse Model during Suppressive Oral Combinational Antiretroviral Therapy." Journal of Virology 92, no. 7 (January 17, 2018): e02118-17. http://dx.doi.org/10.1128/jvi.02118-17.
Full textAbstract:
ABSTRACTAlthough current combinatorial antiretroviral therapy (cART) is therapeutically effective in the majority of HIV patients, interruption of therapy can cause a rapid rebound in viremia, demonstrating the existence of a stable reservoir of latently infected cells. HIV latency is therefore considered a primary barrier to HIV eradication. Identifying, quantifying, and purging the HIV reservoir is crucial to effectively curing patients and relieving them from the lifelong requirement for therapy. Latently infected transformed cell models have been used to investigate HIV latency; however, these models cannot accurately represent the quiescent cellular environment of primary latently infected cellsin vivo. For this reason,in vivohumanized murine models have been developed for screening antiviral agents, identifying latently infected T cells, and establishing treatment approaches for HIV research. Such models include humanized bone marrow/liver/thymus mice and SCID-hu-thy/liv mice, which are repopulated with human immune cells and implanted human tissues through laborious surgical manipulation. However, no one has utilized the human hematopoietic stem cell-engrafted NOD/SCID/IL2rγnull(NSG) model (hu-NSG) for this purpose. Therefore, in the present study, we used the HIV-infected hu-NSG mouse to recapitulate the key aspects of HIV infection and pathogenesisin vivo. Moreover, we evaluated the ability of HIV-infected human cells isolated from HIV-infected hu-NSG mice on suppressive cART to act as a latent HIV reservoir. Our results demonstrate that the hu-NSG model is an effective surgery-freein vivosystem in which to efficiently evaluate HIV replication, antiretroviral therapy, latency and persistence, and eradication interventions.IMPORTANCEHIV can establish a stably integrated, nonproductive state of infection at the level of individual cells, known as HIV latency, which is considered a primary barrier to curing HIV. A complete understanding of the establishment and role of HIV latencyin vivowould greatly enhance attempts to develop novel HIV purging strategies. An ideal animal model for this purpose should be easy to work with, should have a shortened disease course so that efficacy testing can be completed in a reasonable time, and should have immune correlates that are easily translatable to humans. We therefore describe a novel application of the hematopoietic stem cell-transplanted humanized NSG model for dynamically testing antiretroviral treatment, supporting HIV infection, establishing HIV latencyin vivo. The hu-NSG model could be a facile alternative to humanized bone marrow/liver/thymus or SCID-hu-thy/liv mice in which laborious surgical manipulation and time-consuming human cell reconstitution is required.
9
Jones, Clinton. "Herpes Simplex Virus Type 1 and Bovine Herpesvirus 1 Latency." Clinical Microbiology Reviews 16, no. 1 (January 2003): 79–95. http://dx.doi.org/10.1128/cmr.16.1.79-95.2003.
Full textAbstract:
SUMMARY Primary infection by herpes simplex virus type 1 (HSV-1) can cause clinical symptoms in the peripheral and central nervous system, upper respiratory tract, and gastrointestinal tract. Recurrent ocular shedding leads to corneal scarring that can progress to vision loss. Consequently, HSV-1 is the leading cause of corneal blindness due to an infectious agent. Bovine herpesvirus 1 (BHV-1) has similar biological properties to HSV-1 and is a significant health concern to the cattle industry. Latency of BHV-1 and HSV-1 is established in sensory neurons of trigeminal ganglia, but latency can be interrupted periodically, leading to reactivation from latency and spread of infectious virus. The ability of HSV-1 and BHV-1 to reactivate from latency leads to virus transmission and can lead to recurrent disease in individuals latently infected with HSV-1. During latency, the only abundant HSV-1 RNA expressed is the latency-associated transcript (LAT). In latently infected cattle, the latency-related (LR) RNA is the only abundant transcript that is expressed. LAT and LR RNA are antisense to ICP0 or bICP0, viral genes that are crucial for productive infection, suggesting that LAT and LR RNA interfere with productive infection by inhibiting ICP0 or bICP0 expression. Numerous studies have concluded that LAT expression is important for the latency-reactivation cycle in animal models. The LR gene has recently been demonstrated to be required for the latency-reactivation cycle in cattle. Several recent studies have demonstrated that LAT and the LR gene inhibit apoptosis (programmed cell death) in trigeminal ganglia of infected animals and transiently transfected cells. The antiapoptotic properties of LAT map to the same sequences that are necessary for promoting reactivation from latency. This review summarizes our current knowledge of factors regulating the latency-reactivation cycle of HSV-1 and BHV-1.
10
Tibbetts, Scott A., Linda F. van Dyk, Samuel H. Speck, and Herbert W. Virgin. "Immune Control of the Number and Reactivation Phenotype of Cells Latently Infected with a Gammaherpesvirus." Journal of Virology 76, no. 14 (July 15, 2002): 7125–32. http://dx.doi.org/10.1128/jvi.76.14.7125-7132.2002.
Full textAbstract:
ABSTRACT Despite active immune responses, gammaherpesviruses establish latency. In a related process, these viruses also persistently replicate by using a mechanism that requires different viral genes than acute-phase replication. Many questions remain about the role of immunity in chronic gammaherpesvirus infection, including whether the immune system controls latency by regulating latent cell numbers and/or other properties and what specific immune mediators control latency and persistent replication. We show here that CD8+ T cells regulate both latency and persistent replication and demonstrate for the first time that CD8+ T cells regulate both the number of latently infected cells and the efficiency with which infected cells reactivate from latency. Furthermore, we show that gamma interferon (IFN-γ) and perforin, which play no significant role during acute infection, are essential for immune control of latency and persistent replication. Surprisingly, the effects of perforin and IFN-γ are site specific, with IFN-γ being important in peritoneal cells while perforin is important in the spleen. Studies of the mechanisms of action of IFN-γ and perforin revealed that perforin acts primarily by controlling the number of latently infected cells while IFN-γ acts primarily by controlling reactivation efficiency. The immune system therefore controls chronic gammaherpesvirus infection by site-specific mechanisms that regulate both the number and reactivation phenotype of latently infected cells.
11
Hokello, Joseph, Adhikarimayum Lakhikumar Sharma, and Mudit Tyagi. "Combinatorial Use of Both Epigenetic and Non-Epigenetic Mechanisms to Efficiently Reactivate HIV Latency." International Journal of Molecular Sciences 22, no. 7 (April 2, 2021): 3697. http://dx.doi.org/10.3390/ijms22073697.
Full textAbstract:
The persistence of latent HIV provirus pools in different resting CD4+ cell subsets remains the greatest obstacle in the current efforts to treat and cure HIV infection. Recent efforts to purge out latently infected memory CD4+ T-cells using latency-reversing agents have failed in clinical trials. This review discusses the epigenetic and non-epigenetic mechanisms of HIV latency control, major limitations of the current approaches of using latency-reversing agents to reactivate HIV latency in resting CD4+ T-cells, and potential solutions to these limitations.
12
Yang, Zongxing, Jin Yang, Juan Wang, Xiangyun Lu, Changzhong Jin, Tiansheng Xie, and Nanping Wu. "Identify Potential Regulators in HIV-1 Latency by Joint microRNA and mRNA Analysis." Cellular Physiology and Biochemistry 36, no. 2 (2015): 569–84. http://dx.doi.org/10.1159/000430121.
Full textAbstract:
Background/Aims: The main obstacle to cure HIV infection is the existence of long-lasting latent reservoirs. Many efforts have been made to understand basal mechanisms of HIV-1 latency, in which miRNAs play an important role. However, integrated analysis of miRNA and mRNA expression in HIV-1 latency is lacking. Methods and Results: Global miRNA and mRNA expression was determined by microarrays and quantitative reverse transcription PCR in well-characterized HIV-1 latently and actively infected cells, respectively. Interactions of miRNA-mRNA, mRNA-mRNA, and transcription factor-miRNA pairs were assembled into the function network. Our results show that transcription regulation related genes were mostly enriched in HIV-1 latently infected cells. Gene set enrichment analysis revealed nuclear transport related pathways were up-regulated in the latency group. Network dynamic analysis highlighted many gene-pairs sharing the largest changes in different HIV-1 infection state. 83.33% miRNA-target pairs were validated against database, and RHOB related genes constitute the interface between HIV-1 latency and replication state. Conclusion: We show for the first time a joint miRNA and mRNA expression profile related to a HIV-1 latency phenotype, outline a dynamic network of potential regulators involving in HIV-1 latency or replication state, and gain new insights into the source messages for affecting HIV-1 latency.
13
Schaefer, B. C., J. L. Strominger, and S. H. Speck. "Host-cell-determined methylation of specific Epstein-Barr virus promoters regulates the choice between distinct viral latency programs." Molecular and Cellular Biology 17, no. 1 (January 1997): 364–77. http://dx.doi.org/10.1128/mcb.17.1.364.
Full textAbstract:
Epstein-Barr virus (EBV) is capable of adopting three distinct forms of latency: the type III latency program, in which six EBV-encoded nuclear antigens (EBNAs) are expressed, and the type I and type II latency programs, in which only a single viral nuclear protein, EBNA1, is produced. Several groups have reported heavy CpG methylation of the EBV genome in Burkitt's lymphoma cell lines which maintain type I latency, and loss of viral genome methylation in tumor cell lines has been correlated with a switch to type III latency. Here, evidence that the type III latency program must be inactivated by methylation to allow EBV to enter the type I or type II restricted latency program is provided. The data demonstrates that the EBNA1 gene promoter, Qp, active in types I and II latency, is encompassed by a CpG island which is protected from methylation. CpG methylation inactivates the type III latency program and consequently allows the type I or II latency program to operate by alleviating EBNA1-mediated repression of Qp. Methylation of the type III latency EBNA gene promoter, Cp, appears to be essential to prevent type III latency, since EBNA1 is expressed in all latently infected cells and, as shown here, is the only viral antigen required for activation of Cp. EBV is thus a pathogen which subverts host-cell-determined methylation to regulate distinct genetic programs.
14
Perng, Guey-Chuen, Susan M. Slanina, Ada Yukht, Homayon Ghiasi, Anthony B. Nesburn, and Steven L. Wechsler. "The Latency-Associated Transcript Gene Enhances Establishment of Herpes Simplex Virus Type 1 Latency in Rabbits." Journal of Virology 74, no. 4 (February 15, 2000): 1885–91. http://dx.doi.org/10.1128/jvi.74.4.1885-1891.2000.
Full textAbstract:
ABSTRACT The latency-associated transcript (LAT) gene the only herpes simplex virus type 1 (HSV-1) gene abundantly transcribed during neuronal latency, is essential for efficient in vivo reactivation. Whether LAT increases reactivation by a direct effect on the reactivation process or whether it does so by increasing the establishment of latency, thereby making more latently infected neurons available for reactivation, is unclear. In mice, LAT-negative mutants appear to establish latency in fewer neurons than does wild-type HSV-1. However, this has not been confirmed in the rabbit, and the role of LAT in the establishment of latency remains controversial. To pursue this question, we inserted the gene for the enhanced green fluorescent protein (EGFP) under control of the LAT promoter in a LAT-negative virus (ΔLAT-EGFP) and in a LAT-positive virus (LAT-EGFP). Sixty days after ocular infection, trigeminal ganglia (TG) were removed from the latently infected rabbits, sectioned, and examined by fluorescence microscopy. EGFP was detected in significantly more LAT-EGFP-infected neurons than ΔLAT-EGFP-infected neurons (4.9% versus 2%, P < 0.0001). The percentages of EGFP-positive neurons per TG ranged from 0 to 4.6 for ΔLAT-EGFP and from 2.5 to 11.1 for LAT-EGFP (P = 0.003). Thus, LAT appeared to increase neuronal latency in rabbit TG by an average of two- to threefold. These results suggest that LAT enhances the establishment of latency in rabbits and that this may be one of the mechanisms by which LAT enhances spontaneous reactivation. These results do not rule out additional LAT functions that may be involved in maintenance of latency and/or reactivation from latency.
15
Sarabia, Indra, and Alberto Bosque. "HIV-1 Latency and Latency Reversal: Does Subtype Matter?" Viruses 11, no. 12 (November 28, 2019): 1104. http://dx.doi.org/10.3390/v11121104.
Full textAbstract:
Cells that are latently infected with HIV-1 preclude an HIV-1 cure, as antiretroviral therapy does not target this latent population. HIV-1 is highly genetically diverse, with over 10 subtypes and numerous recombinant forms circulating worldwide. In spite of this vast diversity, much of our understanding of latency and latency reversal is largely based on subtype B viruses. As such, most of the development of cure strategies targeting HIV-1 are solely based on subtype B. It is currently assumed that subtype does not influence the establishment or reactivation of latent viruses. However, this has not been conclusively proven one way or the other. A better understanding of the factors that influence HIV-1 latency in all viral subtypes will help develop therapeutic strategies that can be applied worldwide. Here, we review the latest literature on subtype-specific factors that affect viral replication, pathogenesis, and, most importantly, latency and its reversal.
16
Abdalla, Ana Luiza, Gabriel Guajardo-Contreras, and Andrew J. Mouland. "A Canadian Survey of Research on HIV-1 Latency—Where Are We Now and Where Are We Heading?" Viruses 16, no. 2 (February 1, 2024): 229. http://dx.doi.org/10.3390/v16020229.
Full textAbstract:
Worldwide, almost 40 million people are currently living with HIV-1. The implementation of cART inhibits HIV-1 replication and reduces viremia but fails to eliminate HIV-1 from latently infected cells. These cells are considered viral reservoirs from which HIV-1 rebounds if cART is interrupted. Several efforts have been made to identify these cells and their niches. There has been little success in diminishing the pool of latently infected cells, underscoring the urgency to continue efforts to fully understand how HIV-1 establishes and maintains a latent state. Reactivating HIV-1 expression in these cells using latency-reversing agents (LRAs) has been successful, but only in vitro. This review aims to provide a broad view of HIV-1 latency, highlighting Canadian contributions toward these aims. We will summarize the research efforts conducted in Canadian labs to understand the establishment of latently infected cells and how this informs curative strategies, by reviewing how HIV latency is established, which cells are latently infected, what methodologies have been developed to characterize them, how new compounds are discovered and evaluated as potential LRAs, and what clinical trials aim to reverse latency in people living with HIV (PLWH).
17
Perng, Guey-Chuen, and Clinton Jones. "Towards an Understanding of the Herpes Simplex Virus Type 1 Latency-Reactivation Cycle." Interdisciplinary Perspectives on Infectious Diseases 2010 (2010): 1–18. http://dx.doi.org/10.1155/2010/262415.
Full textAbstract:
Infection by herpes simplex virus type 1 (HSV-1) can cause clinical symptoms in the peripheral and central nervous system. Recurrent ocular shedding can lead to corneal scarring and vision loss making HSV-1 a leading cause of corneal blindness due to an infectious agent. The primary site of HSV-1 latency is sensory neurons within trigeminal ganglia. Periodically, reactivation from latency occurs resulting in virus transmission and recurrent disease. During latency, the latency-associated transcript (LAT) is abundantly expressed. LAT expression is important for the latency-reactivation cycle in animal models, in part, because it inhibits apoptosis, viral gene expression, and productive infection. A novel transcript within LAT coding sequences (AL3) and small nonprotein coding RNAs are also expressed in trigeminal ganglia of latently infected mice. In this review, an update of viral factors that are expressed during latency and their potential roles in regulating the latency-reactivation cycle is discussed.
18
Halbhuber, David, Philipp Schauhuber, Valentin Schwind, and Niels Henze. "The Effects of Latency and In-Game Perspective on Player Performance and Game Experience." Proceedings of the ACM on Human-Computer Interaction 7, CHI PLAY (September 29, 2023): 1308–29. http://dx.doi.org/10.1145/3611070.
Full textAbstract:
Previous work shows that high latency, a prolonged delay between player in- and system output, negatively affects player experience and performance. However, previous work also comes to contrary conclusions about how the in-game perspective alters the latency sensitivity of video games. Currently, it is unclear if the in-game perspective independently modulates latency's effects. To investigate how a game's in-game perspective interacts with latency, we developed a shooting game incorporating three perspectives (First-Person-, Third-Person-, and Bird's-Eye-View). In a study, participants (N = 36) played with two levels of latency (low and high) and the three perspectives. We show that latency reduces performance and experience, independent of the perspective. Moreover, Bayesian analysis suggests that the in-game perspective does not interact with latency and does not affects performance or experience. We conclude that more robust means to categorize latency sensitivity of video games than the in-game perspective are required.
19
Nicoll, M. P., J. T. Proença, V. Connor, and S. Efstathiou. "Influence of Herpes Simplex Virus 1 Latency-Associated Transcripts on the Establishment and Maintenance of Latency in the ROSA26R Reporter Mouse Model." Journal of Virology 86, no. 16 (June 13, 2012): 8848–58. http://dx.doi.org/10.1128/jvi.00652-12.
Full textAbstract:
Herpes simplex virus 1 (HSV-1) can establish life-long latent infection in sensory neurons, from which periodic reactivation can occur. During latency, viral gene expression is largely restricted to the latency-associated transcripts (LATs). While not essential for any phase of latency, to date the LATs have been shown to increase the efficiency of both establishment and reactivation of latency in small-animal models. We sought to investigate the role of LAT expression in the frequency of latency establishment within the ROSA26R reporter mouse model utilizing Cre recombinase-encoding recombinant viruses harboring deletions of the core LAT promoter (LAP) region. HSV-1 LAT expression was observed to influence the number of latently infected neurons in trigeminal but not dorsal root ganglia. Furthermore, the relative frequencies of latency establishment of LAT-positive and LAT-negative viruses are influenced by the inoculum dose following infection of the mouse whisker pads. Finally, analysis of the infected cell population at two latent time points revealed a relative loss of latently infected cells in the absence of LAT expression. We conclude that the HSV-1 LATs facilitate the long-term stability of the latent cell population within the infected host and that interpretation of LAT establishment phenotypes is influenced by infection methodology.
20
Knickelbein, Jared E., Kamal M. Khanna, and Robert L. Hendricks. "Lytic granule components are required for the maintenance of HSV-1 neuronal latency (43.35)." Journal of Immunology 178, no. 1_Supplement (April 1, 2007): S43. http://dx.doi.org/10.4049/jimmunol.178.supp.43.35.
Full textAbstract:
Abstract Using a murine model of HSV-1 corneal infection, our data suggest that secretion of CD8 T cell lytic granules (LGs), in addition to IFN-γ, is required for the maintenance of viral latency within trigeminal ganglia (TG). First, HSV-specific CD8 T cells (HSV-CD8), which recognize an immunodominant HSV-1 glycoprotein B (gB498–505) epitope, surround neurons within latently infected TG and contain functional LGs, with GrB polarizing to the contact site with these neurons. HSV-CD8 use GrB and IFN-γ to block HSV-1 reactivation from latency in a non-redundant manner in ex vivo TG cultures, possibly due to a lack of IFN-γ receptors on some latently infected neurons. Like WT mice, Pfn and GrB KO mice establish latency in the TG by 8 days post-infection (dpi) with a similar viral genome copy number, but by 14 dpi, they exhibit a transient rise in viral genome copy number not seen in WT mice suggestive of HSV-1 reactivation from latency. A similar transient rise in copy number is also seen in WT mice depleted of CD8 T cells. Further, neither endogenous CD8 T cells within Pfn KO nor exogenous HSV-CD8 from GrB KO latently infected TG maintain latency as efficiently as CD8 T cells from WT TG in ex vivo TG cultures. Based on the current lack of evidence that CD8 T cell protection leads to neuronal death, we hypothesize a non-lethal LG-mediated block in HSV-1 reactivation from latency and are currently investigating possible mechanisms of protection.
21
Steed, Ashley L., Erik S. Barton, Scott A. Tibbetts, Daniel L. Popkin, Mary L. Lutzke, Rosemary Rochford, and Herbert W. Virgin. "Gamma Interferon Blocks Gammaherpesvirus Reactivation from Latency." Journal of Virology 80, no. 1 (January 1, 2006): 192–200. http://dx.doi.org/10.1128/jvi.80.1.192-200.2006.
Full textAbstract:
ABSTRACT Establishment of latent infection and reactivation from latency are critical aspects of herpesvirus infection and pathogenesis. Interfering with either of these steps in the herpesvirus life cycle may offer a novel strategy for controlling herpesvirus infection and associated disease pathogenesis. Prior studies show that mice deficient in gamma interferon (IFN-γ) or the IFN-γ receptor have elevated numbers of cells reactivating from murine gammaherpesvirus 68 (γHV68) latency, produce infectious virus after the establishment of latency, and develop large-vessel vasculitis. Here, we demonstrate that IFN-γ is a powerful inhibitor of reactivation of γHV68 from latency in tissue culture. In vivo, IFN-γ controls viral gene expression during latency. Importantly, depletion of IFN-γ in latently infected mice results in an increased frequency of cells reactivating virus. This demonstrates that IFN-γ is important for immune surveillance that limits reactivation of γHV68 from latency.
22
Jones, Clinton. "Bovine Herpes Virus 1 (BHV-1) and Herpes Simplex Virus Type 1 (HSV-1) Promote Survival of Latently Infected Sensory Neurons, in Part by Inhibiting Apoptosis." Journal of Cell Death 6 (January 2013): JCD.S10803. http://dx.doi.org/10.4137/jcd.s10803.
Full textAbstract:
α-Herpesvirinae subfamily members, including herpes simplex virus type 1 (HSV-1) and bovine herpes virus 1 (BHV-1), initiate infection in mucosal surfaces. BHV-1 and HSV-1 enter sensory neurons by cell-cell spread where a burst of viral gene expression occurs. When compared to non-neuronal cells, viral gene expression is quickly extinguished in sensory neurons resulting in neuronal survival and latency. The HSV-1 latency associated transcript (LAT), which is abundantly expressed in latently infected neurons, inhibits apoptosis, viral transcription, and productive infection, and directly or indirectly enhances reactivation from latency in small animal models. Three anti-apoptosis genes can be substituted for LAT, which will restore wild type levels of reactivation from latency to a LAT null mutant virus. Two small non-coding RNAs encoded by LAT possess anti-apoptosis functions in transfected cells. The BHV-1 latency related RNA (LR-RNA), like LAT, is abundantly expressed during latency. The LR-RNA encodes a protein (ORF2) and two microRNAs that are expressed in certain latently infected neurons. Wild-type expression of LR gene products is required for stress-induced reactivation from latency in cattle. ORF2 has anti-apoptosis functions and interacts with certain cellular transcription factors that stimulate viral transcription and productive infection. ORF2 is predicted to promote survival of infected neurons by inhibiting apoptosis and sequestering cellular transcription factors which stimulate productive infection. In addition, the LR encoded microRNAs inhibit viral transcription and apoptosis. In summary, the ability of BHV-1 and HSV-1 to interfere with apoptosis and productive infection in sensory neurons is crucial for the life-long latency-reactivation cycle in their respective hosts.
23
Schwerk, Johannes, Lucas Kemper, Kendra A. Bussey, Stefan Lienenklaus, Siegfried Weiss, Luka Čičin-Šain, Andrea Kröger, et al. "Type I Interferon Signaling Controls Gammaherpesvirus Latency In Vivo." Pathogens 11, no. 12 (December 17, 2022): 1554. http://dx.doi.org/10.3390/pathogens11121554.
Full textAbstract:
Gammaherpesviruses, such as Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus, are important human pathogens involved in lymphoproliferative disorders and tumorigenesis. Herpesvirus infections are characterized by a biphasic cycle comprised of an acute phase with lytic replication and a latent state. Murine gammaherpesvirus 68 (MHV-68) is a well-established model for the study of lytic and latent life cycles in the mouse. We investigated the interplay between the type I interferon (IFN)-mediated innate immune response and MHV-68 latency using sensitive bioluminescent reporter mice. Adoptive transfer of latently infected splenocytes into type I IFN receptor-deficient mice led to a loss of latency control. This was revealed by robust viral propagation and dissemination of MHV-68, which coincided with type I IFN reporter induction. Despite MHV-68 latency control by IFN, the continuous low-level cell-to-cell transmission of MHV-68 was detected in the presence of IFN signaling, indicating that IFN cannot fully prevent viral dissemination during latency. Moreover, impaired type I IFN signaling in latently infected splenocytes increased the risk of virus reactivation, demonstrating that IFN directly controls MHV-68 latency in infected cells. Overall, our data show that locally constrained type I IFN responses control the cellular reservoir of latency, as well as the distribution of latent infection to potential new target cells.
24
White, Kirsten Lofgren, Barry Slobedman, and Edward S. Mocarski. "Human Cytomegalovirus Latency-Associated Protein pORF94 Is Dispensable for Productive and Latent Infection." Journal of Virology 74, no. 19 (October 1, 2000): 9333–37. http://dx.doi.org/10.1128/jvi.74.19.9333-9337.2000.
Full textAbstract:
ABSTRACT Human cytomegalovirus latency in bone marrow-derived myeloid progenitors is characterized by the presence of latency-associated transcripts encoded in the ie1/ie2 region of the viral genome. To assess the role of ORF94 (UL126a), a conserved open reading frame on these transcripts, a recombinant virus (RC2710) unable to express this gene was constructed. This virus replicated at wild-type levels and expressed productive as well as latency-associatedie1/ie2 region transcripts. During latency in granulocyte-macrophage progenitors, RC2710 DNA was detected at levels indistinguishable from wild-type virus, latent-phase transcription was present, and RC2710 reactivated when latently infected cells were cocultured with permissive fibroblasts. These data suggest pORF94 is not required for either productive or latent infection as assayed in cultured cells despite being the only known nuclear latency-associated protein.
25
Usherwood, Edward J., Kimberley A. Ward, Marcia A. Blackman, James P. Stewart, and David L. Woodland. "Latent Antigen Vaccination in a Model Gammaherpesvirus Infection." Journal of Virology 75, no. 17 (September 1, 2001): 8283–88. http://dx.doi.org/10.1128/jvi.75.17.8283-8288.2001.
Full textAbstract:
ABSTRACT Vaccines that can reduce the load of latent gammaherpesvirus infections are eagerly sought. One attractive strategy is vaccination against latency-associated proteins, which may increase the efficiency with which T cells recognize and eliminate latently infected cells. However, due to the lack of tractable animal model systems, the effect of latent-antigen vaccination on gammaherpesvirus latency is not known. Here we use the murine gammaherpesvirus model to investigate the impact of vaccination with the latency-associated M2 antigen. As expected, vaccination had no effect on the acute lung infection. However, there was a significant reduction in the load of latently infected cells in the initial stages of the latent infection, when M2 is expressed. These data show for the first time that latent-antigen vaccination can reduce the level of latency in vivo and suggest that vaccination strategies involving other latent antigens may ultimately be successfully used to reduce the long-term latent infection.
26
López, Cinthya Alicia Marcela, Rosa Nicole Freiberger, Franco Agustín Sviercz, Jorge Quarleri, and María Victoria Delpino. "HIV-Infected Hepatic Stellate Cells or HCV-Infected Hepatocytes Are Unable to Promote Latency Reversal among HIV-Infected Mononuclear Cells." Pathogens 13, no. 2 (February 1, 2024): 134. http://dx.doi.org/10.3390/pathogens13020134.
Full textAbstract:
Due to a common mode of transmission through infected human blood, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection is relatively prevalent. In alignment with this, HCV co-infection is associated with an increased size of the HIV reservoir in highly active antiretroviral therapy (HAART)-treated individuals. Hence, it is crucial to comprehend the physiological mechanisms governing the latency and reactivation of HIV in reservoirs. Consequently, our study delves into the interplay between HCV/HIV co-infection in liver cells and its impact on the modulation of HIV latency. We utilized the latently infected monocytic cell line (U1) and the latently infected T-cell line (J-Lat) and found that mediators produced by the infection of hepatic stellate cells and hepatocytes with HIV and HCV, respectively, were incapable of inducing latency reversal under the studied conditions. This may favor the maintenance of the HIV reservoir size among latently infected mononuclear cells in the liver. Further investigations are essential to elucidate the role of the interaction between liver cells in regulating HIV latency and/or reactivation, providing a physiologically relevant model for comprehending reservoir microenvironments in vivo.
27
Sheridan, Brian S., Thomas L. Cherpes, Julie Urban, Pawel Kalinski, and Robert L. Hendricks. "Reevaluating the CD8 T-Cell Response to Herpes Simplex Virus Type 1: Involvement of CD8 T Cells Reactive to Subdominant Epitopes." Journal of Virology 83, no. 5 (December 10, 2008): 2237–45. http://dx.doi.org/10.1128/jvi.01699-08.
Full textAbstract:
ABSTRACT In C57BL/6 (B6) mice, most herpes simplex virus (HSV)-specific CD8 T cells recognize a strongly immunodominant epitope on glycoprotein B (gB498) and can inhibit HSV type 1 (HSV-1) reactivation from latency in trigeminal ganglia (TG). However, half of the CD8 T cells retained in latently infected TG of B6 mice are not gB498 specific and have been largely ignored. The following observations from our current study indicate that these gB498-nonspecific CD8 T cells are HSV specific and may contribute to the control of HSV-1 latency. First, following corneal infection, OVA257-specific OT-1 CD8 T cells do not infiltrate the infected TG unless mice are simultaneously immunized with OVA257 peptide, and then they are not retained. Second, 30% of CD8 T cells in acutely infected TG that produce gamma interferon in response to HSV-1 stimulation directly ex vivo are gB498 nonspecific, and these cells maintain an activation phenotype during viral latency. Finally, gB498-nonspecific CD8 T cells are expanded in ex vivo cultures of latently infected TG and inhibit HSV-1 reactivation from latency in the absence of gB498-specific CD8 T cells. We conclude that many of the CD8 T cells that infiltrate and are retained in infected TG are HSV specific and potentially contribute to maintenance of HSV-1 latency. Identification of the viral proteins recognized by these cells will contribute to a better understanding of the dynamics of HSV-1 latency.
28
Ou, Yang, Kara A. Davis, Vicki Traina-Dorge, and Wayne L. Gray. "Simian Varicella Virus Expresses a Latency-Associated Transcript That Is Antisense to Open Reading Frame 61 (ICP0) mRNA in Neural Ganglia of Latently Infected Monkeys." Journal of Virology 81, no. 15 (May 16, 2007): 8149–56. http://dx.doi.org/10.1128/jvi.00407-07.
Full textAbstract:
ABSTRACT Simian varicella virus (SVV) and varicella-zoster virus (VZV) are closely related alphaherpesviruses that cause varicella (chickenpox) in nonhuman primates and humans, respectively. After resolution of the primary disease, SVV and VZV establish latent infection of neural ganglia and may later reactivate to cause a secondary disease (herpes zoster). This study investigated SVV gene expression in neural ganglia derived from latently infected vervet monkeys. SVV transcripts were detected in neural ganglia, but not in liver or lung tissues, of latently infected animals. A transcript mapping to open reading frame (ORF) 61 (herpes simplex virus type 1 [HSV-1] ICP0 homolog) was consistently detected in latently infected trigeminal, cervical, and lumbar ganglia by reverse transcriptase PCR. Further analysis confirmed that this SVV latency-associated transcript (LAT) was oriented antisense to the gene 61 mRNA. SVV ORF 21 transcripts were also detected in 42% of neural ganglia during latency. In contrast, SVV ORF 28, 29, 31, 62, and 63 transcripts were not detected in ganglia, liver, or lung tissues of latently infected animals. The results demonstrate that viral gene expression is limited during SVV latency and that a LAT antisense to an ICP0 homolog is expressed. In this regard, SVV gene expression during latency is similar to that of HSV-1 and other neurotropic animal alphaherpesviruses but differs from that reported for VZV.
29
Simas, J. Pedro, Sofia Marques, Anne Bridgeman, Stacey Efstathiou, and Heiko Adler. "The M2 gene product of murine gammaherpesvirus 68 is required for efficient colonization of splenic follicles but is not necessary for expansion of latently infected germinal centre B cells." Journal of General Virology 85, no. 10 (October 1, 2004): 2789–97. http://dx.doi.org/10.1099/vir.0.80138-0.
Full textAbstract:
Infection of mice with murine gammaherpesvirus 68 is characterized by a marked transient expansion of latently infected splenic germinal centre (GC) B cells, which is followed by lower levels of persistent infection in GC and memory B cells. Virus transcription within GC B cells is restricted to a number of latency-associated open reading frames, including M2. This gene encodes a structurally unique protein of unknown function, which has been shown to be essential for the transient peak of virus latency during the establishment of latent infection in the spleen. This study shows that upon infection of mice with M2-defective viruses, at 14 days post-infection during the establishment of latency in the spleen, there was a reduction in the number of latently infected follicles when compared with wild-type virus. However, the mean number of latently infected cells within each follicle was equivalent between wild-type and M2-defective viruses. Late in infection, disruption of M2 resulted in sustained and abnormally high levels of virus persistence in splenic GC B cells but not memory B cells. These data indicate that during the establishment of latency in the spleen, the M2 gene product is required for efficient colonization of splenic follicles but is dispensable for the expansion of latently infected GC B cells and that M2 might be a critical modulator of B-cell function.
30
Zabarain Cogollo, Sara, Liliana Quintero Díaz, and Ana Rita Russo De Vivo. "Logros del yo durante el desarrollo psicoafectivo en la etapa de latencia. Achievements of the self during the psychoaffective development in the latency stage." Psicoespacios 9, no. 14 (June 26, 2015): 129. http://dx.doi.org/10.25057/21452776.342.
Full textAbstract:
Achievements of the self during the psychoaffective development in the latency stage. Resumen Este artículo es el producto de la revisión de referencias del desarrollo psicoafectivo en la etapa de latencia. Los logros del yo en la latencia temprana se encuentran relacionados con el control de los impulsos, la represión de los impulsos sexuales, dando paso a la formación reactiva y la sublimación que se orienta hacia el desarrollo de metas y, los logros del yo en la latencia tardía se dan en torno al desarrollo de un proceso de autonomía, incremento del proceso secundario de pensamiento y mayor acercamiento hacia las relaciones con pares. Las actividades en la etapa de latencia, se dirigen hacia fines de tipo intelectual, que permiten el desarrollo de habilidades sociales y la construcción colectiva de nuevos aprendizajes que proporciona la escolarización. Infortunadamente los niños de Colombia se enfrentan a la negligencia de parte de las instituciones educativas, que no atienden adecuadamente las demandas que se requieren para una apropiada formación, para lo cual es importante, se tengan en cuenta los procesos individuales y grupales que se necesitan para el desarrollo de la autocrítica y del pensamiento. Palabras claves: Desarrollo psicoafectivo, etapa de latencia, relaciones con pares Summary This article is the result of the review of references of psycho development in the latency stage. The achievements of the self in early latency are related to impulse control, repression of sexual impulses, leading to reaction formation and sublimation that is geared towards the development of goals and achievements of the self in late latency are given on the development of a process of autonomy, increased secondary thought process and closer towards relationships with peers. Activities in the latency stage, head towards the end of intellectual, allowing the development of social skills and the collective construction of new learning that provides schooling. Unfortunately the children of Colombia faced with the negligence of educational institutions, which do not adequately address the demands that are required for proper training, for which it is important, individual and group processes that need to be taken into account development of self-criticism and thought. Keywords: Developing psycho, latency stage, peer group.
31
Ukah, Obiaara, Maritza Puray-Chavez, Philip Tedbury, Alon Herschhorn, Joseph Sodroski, and Stefan Sarafianos. "Visualization of HIV-1 RNA Transcription from Integrated HIV-1 DNA in Reactivated Latently Infected Cells." Viruses 10, no. 10 (September 30, 2018): 534. http://dx.doi.org/10.3390/v10100534.
Full textAbstract:
We have recently developed the first microscopy-based strategy that enables simultaneous multiplex detection of viral RNA (vRNA), viral DNA (vDNA), and viral protein. Here, we used this approach to study the kinetics of latency reactivation in cells infected with the human immunodeficiency virus (HIV). We showed the transcription of nascent vRNA from individual latently integrated and reactivated vDNA sites appearing earlier than viral protein. We further demonstrated that this method can be used to quantitatively assess the efficacy of a variety of latency reactivating agents. Finally, this microscopy-based strategy was augmented with a flow-cytometry-based approach, enabling the detection of transcriptional reactivation of large numbers of latently infected cells. Hence, these approaches are shown to be suitable for qualitative and quantitative studies of HIV-1 latency and reactivation.
32
Duggan, Natasha N., Tatjana Dragic, Sumit K. Chanda, and Lars Pache. "Breaking the Silence: Regulation of HIV Transcription and Latency on the Road to a Cure." Viruses 15, no. 12 (December 15, 2023): 2435. http://dx.doi.org/10.3390/v15122435.
Full textAbstract:
Antiretroviral therapy (ART) has brought the HIV/AIDS epidemic under control, but a curative strategy for viral eradication is still needed. The cessation of ART results in rapid viral rebound from latently infected CD4+ T cells, showing that control of viral replication alone does not fully restore immune function, nor does it eradicate viral reservoirs. With a better understanding of factors and mechanisms that promote viral latency, current approaches are primarily focused on the permanent silencing of latently infected cells (“block and lock”) or reactivating HIV-1 gene expression in latently infected cells, in combination with immune restoration strategies to eliminate HIV infected cells from the host (“shock and kill”). In this review, we provide a summary of the current, most promising approaches for HIV-1 cure strategies, including an analysis of both latency-promoting agents (LPA) and latency-reversing agents (LRA) that have shown promise in vitro, ex vivo, and in human clinical trials to reduce the HIV-1 reservoir.
33
Marinšek, Alexander, Daan Delabie, Lieven De Strycker, and Liesbet Van der Perre. "Physical Layer Latency Management Mechanisms: A Study for Millimeter-Wave Wi-Fi." Electronics 10, no. 13 (July 3, 2021): 1599. http://dx.doi.org/10.3390/electronics10131599.
Full textAbstract:
Emerging applications in fields such as extended reality require both a high throughput and low latency. The millimeter-wave (mmWave) spectrum is considered because of the potential in the large available bandwidth. The present work studies mmWave Wi-Fi physical layer latency management mechanisms, a key factor in providing low-latency communications for time-critical applications. We calculate physical layer latency in an ideal scenario and simulate it using a tailor-made simulation framework, based on the IEEE 802.11ad standard. Assessing data reception quality over a noisy channel yielded latency’s dependency on transmission parameters, channel noise, and digital baseband tuning. Latency in function of the modulation and coding scheme was found to span 0.28–2.71 ms in the ideal scenario, whereas simulation results also revealed its tight bond with the demapping algorithm and the number of low-density parity-check decoder iterations. The findings yielded tuning parameter combinations for reaching Pareto optimality either by constraining the bit error rate and optimizing latency or the other way around. Our assessment shows that trade-offs can and have to be made to provide sufficiently reliable low-latency communication. In good channel conditions, one may benefit from both the very high throughput and low latency; yet, in more adverse situations, lower modulation orders and additional coding overhead are a necessity.
34
Rutherglen, Michael. "Latency." Literary Imagination 22, no. 1 (January 11, 2020): 91. http://dx.doi.org/10.1093/litimag/imz066.
Full text
35
Gangappa, Shivaprakash, Sharookh B. Kapadia, Samuel H. Speck, and Herbert W. Virgin. "Antibody to a Lytic Cycle Viral Protein Decreases Gammaherpesvirus Latency in B-Cell-Deficient Mice." Journal of Virology 76, no. 22 (November 15, 2002): 11460–68. http://dx.doi.org/10.1128/jvi.76.22.11460-11468.2002.
Full textAbstract:
ABSTRACT While antiviral antibody plays a key role in resistance to acute viral infection, the contribution of antibody to the control of latent virus infection is less well understood. Gammaherpesvirus 68 (γHV68) infection of mice provides a model well suited to defining contributions of specific immune system components to the control of viral latency. B cells play a critical role in regulating γHV68 latency, but the mechanism(s) by which B cells regulate latency is not known. In the experiments reported here, we determined the effect of passively transferred antibody on established γHV68 latency in B-cell-deficient (B-cell−/−) mice. Immune antibody decreased the frequency of cells reactivating ex vivo from latency in splenocytes (>10-fold) and peritoneal cells (>100-fold) and the frequency of cells carrying latent viral genome in splenocytes (>5-fold) and peritoneal cells (>50-fold). This effect required virus-specific antibody and was observed when total and virus-specific serum antibody concentrations in recipient B-cell−/− mice were <8% of those in normal mice during latent infection. Passive transfer of antibody specific for the lytic cycle γHV68 RCA protein, but not passive transfer of antibody specific for the v-cyclin protein or the latent protein M2, decreased both the frequency of cells reactivating ex vivo from latency and the frequency of cells carrying the latent viral genome. Therefore, antibody specific for lytic cycle viral antigens can play an important role in the control of gammaherpesvirus latency in immunocompromised hosts. Based on these findings, we propose a model in which ongoing productive replication is essential for maintaining high levels of latently infected cells in immunocompromised hosts. We confirmed this model by the treatment of latently infected B-cell−/− mice with the antiviral drug cidofovir.
36
Inman, Melissa, Joe Zhou, Heather Webb, and Clinton Jones. "Identification of a Novel Bovine Herpesvirus 1 Transcript Containing a Small Open Reading Frame That Is Expressed in Trigeminal Ganglia of Latently Infected Cattle." Journal of Virology 78, no. 10 (May 15, 2004): 5438–47. http://dx.doi.org/10.1128/jvi.78.10.5438-5447.2004.
Full textAbstract:
ABSTRACT Bovine herpesvirus 1 (BHV-1), like other Alphaherpesvirinae subfamily members, establishes latency in sensory neurons. The latency-related (LR) RNA is abundantly expressed during latency, and expression of an LR protein is required for the latency reactivation cycle in cattle. Within LR promoter sequences, a 135-amino-acid open reading frame (ORF) was identified, ORF-E, that is antisense to the LR RNA. ORF-E is also downstream of the gene encoding the major viral transcriptional activator, bICP0. Strand-specific reverse transcription-PCR demonstrated that a transcript containing ORF-E was consistently expressed in trigeminal ganglia (TG) of latently infected calves, productively infected cultured cells, and acutely infected calves. As expected, a late transcript encoding glycoprotein C was not detected in TG of latently infected calves. The ORF-E transcript is polyadenylated and is expressed early when cultured bovine cells are productively infected. Protein coding sequences containing ORF-E were fused to green fluorescent protein (GFP) to examine the cellular localization of the putative protein. In transiently transfected mouse neuroblastoma (neuro-2A) and human neuroblastoma (SK-N-SH) cells, the ORF-E/GFP fusion protein was detected in discreet domains within the nucleus. In contrast, the ORF-E/GFP fusion protein was detected in the cytoplasm and nucleus of rabbit skin cells and bovine kidney cells. As expected, the GFP protein was expressed in the cytoplasm and nucleus of transfected cells. These studies indicate that the ORF-E transcript is consistently expressed during latency. We suggest that the ORF-E gene regulates some aspect of the latency reactivation cycle.
37
Kondo, Kazuhiro, Kazuya Shimada, Junji Sashihara, Keiko Tanaka-Taya, and Koichi Yamanishi. "Identification of Human Herpesvirus 6 Latency-Associated Transcripts." Journal of Virology 76, no. 8 (April 15, 2002): 4145–51. http://dx.doi.org/10.1128/jvi.76.8.4145-4151.2002.
Full textAbstract:
ABSTRACT Four kinds of latency-associated transcripts of human herpesvirus 6 were identified which were detected only in latently infected cells. Although they were oriented in the same direction as the immediate-early 1 and 2 (IE1/IE2) genes and shared their protein-coding region with IE1/IE2, their transcription start sites and exon(s) were latency associated.
38
Ge, Jun Wei, Hai Ming Zheng, and Yi Qiu Fang. "A Hybird Virtual Machine Placement Aglrithm for Virtualized Desktop Infrastructure." Advanced Materials Research 760-762 (September 2013): 1906–10. http://dx.doi.org/10.4028/www.scientific.net/amr.760-762.1906.
Full textAbstract:
As we all kown, The virtual machine placement is one kind of bin-packing problem. By optimizing placement of virtual machine. We can improve VM performance, enhance resource utilization, reduce energy comsumption. After analysis the existing virtual machine placement aglrithm. We propose a hybird virtual machine placement aglrithm (HTA) which based on network latency threshold for the requirement of low network latence and low VM migraiton ratio in Virtualized Desktop Infrastructure. It elect qualified node set based on network latency threshold and palce the virtual machines with load-balance policy, taking into account the preformance of the network and vitual machines. According to analysis and comparison. The simulation result show that the algorithm can effectively lessen the network latency and reduce the VM migration ratio.
39
Poole, Emma, Jonathan Lau, Ian Groves, Kate Roche, Eain Murphy, Maria Carlan da Silva, Matthew Reeves, and John Sinclair. "The Human Cytomegalovirus Latency-Associated Gene Product Latency Unique Natural Antigen Regulates Latent Gene Expression." Viruses 15, no. 9 (September 4, 2023): 1875. http://dx.doi.org/10.3390/v15091875.
Full textAbstract:
Human cytomegalovirus (HCMV) infection can lead to either lytic or latent infection, which is dependent on the regulation of the viral major immediate early promoter (MIEP). Suppression of the MIEP is a pre-requisite for latency and is driven by repressive epigenetic modifications at the MIEP during latent infection. However, other viral genes are expressed during latency and this is correlated with activatory epigenetic modifications at latent gene promoters. Yet the molecular basis of the differential regulation of latent and lytic gene expression by epigenetics is unclear. LUNA, a latent viral transcript, has been suggested to be important for HCMV latency and has also been shown to be important for efficient reactivation likely through its known deSUMOylase activity. Intriguingly, we and others have also observed that LUNA enhances latency-associated expression of the viral UL138 gene. Here, we show that in the absence of LUNA, the expression of multiple latency-associated transcripts is reduced during latent infection, which is correlated with a lack of activatory marks at their promoters. Interestingly, we also show that LUNA interacts with the hematopoietic transcription factor GATA-2, which has previously been shown to bind to a number of latency-associated gene promoters, and that this interaction is dependent on the deSUMOylase domain of LUNA. Finally, we show that the deSUMOylase activity of LUNA is required for the establishment and/or maintenance of an open chromatin configuration around latency-associated gene promoters. As such, LUNA plays a key role in efficient latency-associated viral gene expression and carriage of viral genome during latent carriage.
40
FAROOQ, SHEZA, AMAN KUMAR, SUMAN CHAUDHARY, and SUSHILA MAAN. "Development of TaqMan probe-based RT-qPCR assays for detection of BoHV-1 latency in Bovine." Indian Journal of Animal Sciences 94, no. 3 (March 11, 2024): 247–50. http://dx.doi.org/10.56093/ijans.v94i3.143188.
Full textAbstract:
Bovine herpesvirus-1 is highly contagious virus of cattle and buffaloes all over the world. It establishes lifelong latency in ganglionic neurons of the peripheral nervous system. Since, trigeminal ganglia are the main sites of latency, therefore, it is challenging to detect BoHV-1 in latently infected live animals. No research work has been done to correlate the sero-prevalence and latency in peripheral blood mononuclear cells (PBMC). The present study was designed to detect BoHV-1 latency related transcript or microRNA in peripheral blood mononuclear cells of sero-positive animals. The highly sensitive RT-qPCR assays based on TaqMan chemistry have been developed for the detection of transcripts of BoHV-1 latency. The limit of detection (LOD) of the assays for ORF-1 specific RT-qPCR and miRNA specific RT-qPCR was 460 copies and 117 copies respectively. The efficiency of the developed assays was 93.5% for ORF-1 and 97.93% for miRNA transcript. None of the PBMC samples of seropositive animals found positive for ORF-1 and miRNA transcripts in developed assays.The absence of latency specific transcripts in PBMC might be due to very low expression i.e. beyond the LOD of newly developed assays or absence of latency in PBMC of seropositive animal. However, further studies are required to establish the fact. To the best of authors knowledge, this is the first report of latency-specific RT-qPCR assay development and its application in PBMC of BoHV-1 seropositive cattle.
41
Sadaoka, Tomohiko, Daniel P. Depledge, Labchan Rajbhandari, Arun Venkatesan, Judith Breuer, and Jeffrey I. Cohen. "In vitro system using human neurons demonstrates that varicella-zoster vaccine virus is impaired for reactivation, but not latency." Proceedings of the National Academy of Sciences 113, no. 17 (April 12, 2016): E2403—E2412. http://dx.doi.org/10.1073/pnas.1522575113.
Full textAbstract:
Varicella-zoster virus (VZV) establishes latency in human sensory and cranial nerve ganglia during primary infection (varicella), and the virus can reactivate and cause zoster after primary infection. The mechanism of how the virus establishes and maintains latency and how it reactivates is poorly understood, largely due to the lack of robust models. We found that axonal infection of neurons derived from hESCs in a microfluidic device with cell-free parental Oka (POka) VZV resulted in latent infection with inability to detect several viral mRNAs by reverse transcriptase-quantitative PCR, no production of infectious virus, and maintenance of the viral DNA genome in endless configuration, consistent with an episome configuration. With deep sequencing, however, multiple viral mRNAs were detected. Treatment of the latently infected neurons with Ab to NGF resulted in production of infectious virus in about 25% of the latently infected cultures. Axonal infection of neurons with vaccine Oka (VOka) VZV resulted in a latent infection similar to infection with POka; however, in contrast to POka, VOka-infected neurons were markedly impaired for reactivation after treatment with Ab to NGF. In addition, viral transcription was markedly reduced in neurons latently infected with VOka compared with POka. Our in vitro system recapitulates both VZV latency and reactivation in vivo and may be used to study viral vaccines for their ability to establish latency and reactivate.
42
Workman, Aspen, Sandra Perez, Alan Doster, and Clinton Jones. "Dexamethasone Treatment of Calves Latently Infected with Bovine Herpesvirus 1 Leads to Activation of the bICP0 Early Promoter, in Part by the Cellular Transcription Factor C/EBP-Alpha." Journal of Virology 83, no. 17 (June 24, 2009): 8800–8809. http://dx.doi.org/10.1128/jvi.01009-09.
Full textAbstract:
ABSTRACT Sensory neurons within trigeminal ganglia (TG) are the primary site for bovine herpesvirus 1 (BHV-1) latency. During latency, viral gene expression is restricted to the latency-related (LR) gene and the open reading frame ORF-E. We previously constructed an LR mutant virus that expresses LR RNA but not any of the known LR proteins. In contrast to calves latently infected with wild-type (wt) BHV-1 or the LR rescued virus, the LR mutant virus does not reactivate from latency following dexamethasone (DEX) treatment. In this study, we demonstrated that bICP0, but not bICP4, transcripts were consistently detected in TG of calves infected with the LR mutant or LR rescued virus following DEX treatment. Calves latently infected with the LR rescued virus but not the LR mutant virus expressed late transcripts, which correlated with shedding of infectious virus following DEX treatment. The bICP4 and bICP0 genes share a common immediate-early promoter, suggesting that this promoter was not consistently activated during DEX-induced reactivation from latency. The bICP0 gene also contains a novel early promoter that was activated by DEX in mouse neuroblastoma cells. Expression of a cellular transcription factor, C/EBP-alpha, was stimulated by DEX, and C/EBP-alpha expression was necessary for DEX induction of bICP0 early promoter activity. C/EBP-alpha directly interacted with bICP0 early promoter sequences that were necessary for trans activation by C/EBP-alpha. In summary, DEX treatment of latently infected calves induced cellular factors that stimulated bICP0 early promoter activity. Activation of bICP0 early promoter activity does not necessarily lead to late gene expression and virus shedding.
43
Nampala, Hasifa, Matylda Jablonska-Sabuka, and Martin Singull. "Mathematical Analysis of the Role of HIV/HBV Latency in Hepatocytes." Journal of Applied Mathematics 2021 (November 17, 2021): 1–15. http://dx.doi.org/10.1155/2021/5525857.
Full textAbstract:
The biggest challenge of treating HIV is rampant liver-related morbidity and mortality. This is, to some extent, attributed to hepatocytes acting as viral reservoirs to both HIV and HBV. Viral reservoirs harbour latent provirus, rendering it inaccessible by combinational antiretroviral therapy (cART) that is specific to actively proliferating virus. Latency reversal agents (LRA) such as Shock and kill or lock and block, aiming at activating the latently infected cells, have been developed. However, they are CD4+ cell-specific only. There is evidence that the low replication level of HIV in hepatocytes is mainly due to the latency of the provirus in these cells. LRA are developed to reduce the number of latently infected cells; however, the impact of the period viral latency in hepatocytes especially, during HIV/HBV coinfection, needs to be investigated. Viral coinfection coupled with lifelong treatment of HIV/HBV necessitates investigation for the optimal control strategy. We propose a coinfection mathematical model with delay and use optimal control theory to analyse the effect of viral latency in hepatocytes on the dynamics of HIV/HBV coinfection. Analytical results indicate that HBV cannot take a competitive exclusion against HIV; thus, the coinfection endemic equilibrium implies chronic HBV in HIV-infected patients. Numerical and analytical results indicate that both HIV and HBV viral loads are higher with longer viral latency period in hepatocytes, which indicates the need to upgrade LRA to other non-CD4+ cell viral reservoirs. Higher viral load caused by viral latency coupled with the effects of cART partly explains why liver-related complications are the leading cause of mortality in HIV-infected persons.
44
Mott, Kevin R., Catherine J. Bresee, Sariah J. Allen, Lbachir BenMohamed, Steven L. Wechsler, and Homayon Ghiasi. "Level of Herpes Simplex Virus Type 1 Latency Correlates with Severity of Corneal Scarring and Exhaustion of CD8+ T Cells in Trigeminal Ganglia of Latently Infected Mice." Journal of Virology 83, no. 5 (December 17, 2008): 2246–54. http://dx.doi.org/10.1128/jvi.02234-08.
Full textAbstract:
ABSTRACT A hallmark of infection with herpes simplex virus type 1 (HSV-1) is the establishment of latency in ganglia of the infected individual. During the life of the latently infected individual, the virus can occasionally reactivate, travel back to the eye, and cause recurrent disease. Indeed, a major cause of corneal scarring (CS) is the scarring induced by HSV-1 following reactivation from latency. In this study, we evaluated the relationship between the amount of CS and the level of the HSV-1 latency-associated transcript (LAT) in trigeminal ganglia (TG) of latently infected mice. Our results suggested that the amount of CS was not related to the amount of virus replication following primary ocular HSV-1 infection, since replication in the eyes was similar in mice that did not develop CS, mice that developed CS in just one eye, and mice that developed CS in both eyes. In contrast, mice with no CS had significantly less LAT, and thus presumably less latency, in their TG than mice that had CS in both eyes. Higher CS also correlated with higher levels of mRNAs for PD-1, CD4, CD8, F4/80, interleukin-4, gamma interferon, granzyme A, and granzyme B in both cornea and TG. These results suggest that (i) the immunopathology induced by HSV-1 infection does not correlate with primary virus replication in the eye; (ii) increased CS appears to correlate with increased latency in the TG, although the possible cause-and-effect relationship is not known; and (iii) increased latency in mouse TG correlates with higher levels of PD-1 mRNA, suggesting exhaustion of CD8+ T cells.
45
Jaber, Tareq, Aspen Workman, and Clinton Jones. "Small Noncoding RNAs Encoded within the Bovine Herpesvirus 1 Latency-Related Gene Can Reduce Steady-State Levels of Infected Cell Protein 0 (bICP0)." Journal of Virology 84, no. 13 (April 21, 2010): 6297–307. http://dx.doi.org/10.1128/jvi.02639-09.
Full textAbstract:
ABSTRACT Following acute infection in mucosal epithelium, bovine herpes virus 1 (BHV-1) establishes lifelong latency in sensory neurons within trigeminal ganglia. The latency-related RNA (LR-RNA) is abundantly expressed in sensory neurons of latently infected calves. Expression of LR proteins is necessary for the latency reactivation cycle because a mutant virus that does not express LR proteins is unable to reactivate from latency after dexamethasone treatment. LR-RNA sequences also inhibit bICP0 expression, productive infection, and cell growth. However, it is unclear how LR-RNA mediates these functions. In this study, we identified a 463-bp region within the LR gene (the XbaI-PstI [XP] fragment) that inhibited bICP0 protein and RNA expression in transiently transfected mouse neuroblastoma cells. Small noncoding RNAs (sncRNAs) encoded within the XP fragment (20 to 90 nucleotides in length) were detected in transiently transfected mouse neuroblastoma cells. Two families of sncRNAs were cloned from this region, and each family was predicted to contain a mature microRNA (miRNA). Both miRNAs were predicted to base pair with bICP0 mRNA sequences, suggesting that they reduce bICP0 levels. To test this prediction, sequences encompassing the respective sncRNAs and mature miRNAs were synthesized and cloned into a small interfering RNA expression vector. Both sncRNA families and their respective miRNAs inhibited bICP0 protein expression in mouse neuroblastoma cells and productive infection in bovine cells. In trigeminal ganglia of latently infected calves, an sncRNA that migrated between nucleotides 20 and 25 hybridized to the XP fragment. During dexamethasone-induced reactivation from latency, XP-specific sncRNA levels were reduced, suggesting that these sncRNAs support the establishment and maintenance of lifelong latency in cattle.
46
Krishna, Benjamin A., Amanda B. Wass, and Christine M. O’Connor. "The AP-1 Transcription Factor Is a Key Determinant of Human Cytomegalovirus Latency and Reactivation." Proceedings 50, no. 1 (July 13, 2020): 127. http://dx.doi.org/10.3390/proceedings2020050127.
Full textAbstract:
Human cytomegalovirus (HCMV) is a ubiquitous pathogen that latently infects hematopoietic progenitor cells (HPCs). Individuals with a competent immune system are, for the most part, asymptomatic for the disease. However when a latently infected individual becomes immunosuppressed, HCMV can reactivate, causing severe morbidity and mortality. While much of the viral genome is transcriptionally silenced during latency, some genes are expressed, including the HCMV-encoded G-protein coupled receptor US28. We showed that US28 expression is required for latency, as it suppressed the activator protein-1 (AP-1) transcription factor by attenuating the AP-1 subunit, fos. In turn, this prevents AP-1 from binding and activating the major immediate early promoter (MIEP), the key promoter regulating the latent-to-lytic transcriptional “switch”. Our new data suggest that US28-mediated signaling during latency attenuates the Src-MAPK signaling axis to regulate AP-1. We find that US28 expression suppresses Src, MEK, and ERK, as well as fos phosphorylation and AP-1 binding to the MIEP. Conversely, the pharmacological inhibition of Src, MEK, or ERK in US28Δ-latently infected HPCs suppresses infectious virus production, demonstrating the important role for this signaling axis during latency. Our recent data also reveal that regulating AP-1 is a key determinant in balancing HCMV latency and reactivation. Infection with a virus in which we disrupted the proximal AP-1 binding site in the MIEP (AP-1Δp) leads to reduced AP-1 binding and inefficient viral reactivation compared to wild type. Furthermore, AP-1 is critical for the de-repression of MIEP-driven transcripts and downstream early and late genes, while other immediate early genes remain unaffected. Collectively, these data suggest that AP-1 binding to the MIEP is suppressed during latency, but is required for the efficient transactivation of the MIEP during reactivation. We are currently elucidating US28’s involvement in recruiting AP-1 to the MIEP during reactivation.
47
Cohen, Jeffrey I., Tammy Krogmann, Jeffrey P. Ross, Lesley Pesnicak, and Elena A. Prikhod'ko. "Varicella-Zoster Virus ORF4 Latency-Associated Protein Is Important for Establishment of Latency." Journal of Virology 79, no. 11 (June 1, 2005): 6969–75. http://dx.doi.org/10.1128/jvi.79.11.6969-6975.2005.
Full textAbstract:
ABSTRACT Varicella-zoster virus (VZV) encodes at least six genes that are expressed during latency. One of the genes, ORF4, encodes an immediate-early protein that is present in the virion tegument. ORF4 RNA and protein have been detected in latently infected human ganglia. We have constructed a VZV mutant deleted for ORF4 and have shown that the gene is essential for replication in vitro. The ORF4 mutant virus could be propagated when grown in cells infected with baculovirus expressing the ORF4 protein under the human cytomegalovirus immediate-early promoter. In contrast, the VZV ORF4 deletion mutant could not be complemented in cells expressing herpes simplex virus type 1 (HSV-1) ICP27, the homolog of ORF4. Cells infected with baculovirus expressing ORF4 did not complement an HSV-1 ICP27 deletion mutant. VZV-infected cotton rats have been used as a model for latency; viral DNA and latency-associated transcripts are expressed in dorsal root ganglia 1 month or more after experimental infection. Cotton rats inoculated with VZV lacking ORF4 showed reduced frequency of latency compared to animals infected with the parental or ORF4-rescued virus. Thus, in addition to VZV ORF63, which was previously shown to be critical for efficient establishment of latency, ORF4 is also important for latent infection.
48
Roughan, Jill E., and David A. Thorley-Lawson. "The Intersection of Epstein-Barr Virus with the Germinal Center." Journal of Virology 83, no. 8 (February 4, 2009): 3968–76. http://dx.doi.org/10.1128/jvi.02609-08.
Full textAbstract:
ABSTRACT The current model of Epstein-Barr virus (EBV) infection and persistence in vivo proposes that EBV uses the germinal center (the GC model) to establish a quiescent latent infection in otherwise-normal memory B cells. However, the evidence linking EBV-infected cells and the GC is only indirect and limited. Therefore, a key portion of the model, that EBV-infected cells physically reside and participate in GCs, has yet to be verified. Furthermore, recent experiments suggested that upon infection of GC cells the viral growth latency transcription program is dominant and GC functionality and phenotype are ablated, i.e., EBV infection is not consistent with GC function. In this study we show that in vivo, EBV-infected B cells in the tonsils retain expression of functional and phenotypic markers of GC cells, including bcl-6 and AID. Furthermore, these cells are physically located in the GC and express a restricted form of latency, the default latency program. Thus, the EBV default latency transcription program, unlike the growth latency program, is consistent with the retention of GC functionality in vivo. This work verifies key components of the GC model of EBV persistence and suggests that EBV and the GC can interact to produce the latently infected memory cells found in the periphery. Furthermore, it identifies latently infected GC B cells as a potential pathogenic nexus for the development of the EBV-positive, GC-associated lymphomas Hodgkin's disease and Burkitt's lymphoma.
49
Taura, Manabu, Eriko Kudo, Ryusho Kariya, Hiroki Goto, Kouki Matsuda, Shinichiro Hattori, Kulthida Vaeteewoottacharn, et al. "COMMD1/Murr1 Reinforces HIV-1 Latent Infection through IκB-α Stabilization." Journal of Virology 89, no. 5 (December 17, 2014): 2643–58. http://dx.doi.org/10.1128/jvi.03105-14.
Full textAbstract:
ABSTRACTThe transcription factor NF-κB is important for HIV-1 transcription initiation in primary HIV-1 infection and reactivation in latently HIV-1-infected cells. However, comparative analysis of the regulation and function of NF-κB in latently HIV-1-infected cells has not been done. Here we show that the expression of IκB-α, an endogenous inhibitor of NF-κB, is enhanced by latent HIV-1 infection via induction of the host-derived factor COMMD1/Murr1 in myeloid cells but not in lymphoid cells by using four sets of latently HIV-1-infected cells and the respective parental cells. IκB-α protein was stabilized by COMMD1, which attenuated NF-κB signaling during Toll-like receptor ligand and tumor necrosis factor alpha treatment and enhanced HIV-1 latency in latently HIV-1-infected cells. Activation of the phosphoinositol 3-kinase (PI3K)–JAK pathway is involved in COMMD1 induction in latently HIV-1-infected cells. Our findings indicate that COMMD1 induction is the NF-κB inhibition mechanism in latently HIV-1-infected cells that contributes to innate immune deficiency and reinforces HIV-1 latency. Thus, COMMD1 might be a double-edged sword that is beneficial in primary infection but not beneficial in latent infection when HIV-1 eradication is considered.IMPORTANCEHIV-1 latency is a major barrier to viral eradication in the era of combination antiretroviral therapy. In this study, we found that COMMD1/Murr1, previously identified as an HIV-1 restriction factor, inhibits the proteasomal degradation of IκB-α by increasing the interaction with IκB-α in latently HIV-1-infected myeloid cells. IκB-α protein was stabilized by COMMD1, which attenuated NF-κB signaling during the innate immune response and enhanced HIV-1 latency in latently HIV-1-infected cells. Activation of the PI3K-JAK pathway is involved in COMMD1 induction in latently HIV-1-infected cells. Thus, the host-derived factor COMMD1 is beneficial in suppressing primary infection but enhances latent infection, indicating that it may be a double-edged sword in HIV-1 eradication.
50
Giordani, Nicole V., Donna M. Neumann, Dacia L. Kwiatkowski, Partha S. Bhattacharjee, Peterjon K. McAnany, James M. Hill, and David C. Bloom. "During Herpes Simplex Virus Type 1 Infection of Rabbits, the Ability To Express the Latency-Associated Transcript Increases Latent-Phase Transcription of Lytic Genes." Journal of Virology 82, no. 12 (April 9, 2008): 6056–60. http://dx.doi.org/10.1128/jvi.02661-07.
Full textAbstract:
ABSTRACT Trigeminal ganglia (TG) from rabbits latently infected with either wild-type herpes simplex virus type 1 (HSV-1) or the latency-associated transcript (LAT) promoter deletion mutant 17ΔPst were assessed for their viral chromatin profile and transcript abundance. The wild-type 17syn+ genomes were more enriched in the transcriptionally permissive mark dimethyl H3 K4 than were the 17ΔPst genomes at the 5′ exon and ICP0 and ICP27 promoters. Reverse transcription-PCR analysis revealed significantly more ICP4, tk, and glycoprotein C lytic transcripts in 17syn+ than in 17ΔPst. These results suggest that, for efficient reactivation from latency in rabbits, the LAT is important for increased transcription of lytic genes during latency.