Journal articles on the topic 'Lentivirusus'
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1
Clements, J. E., and M. C. Zink. "Molecular biology and pathogenesis of animal lentivirus infections." Clinical Microbiology Reviews 9, no. 1 (January 1996): 100–117. http://dx.doi.org/10.1128/cmr.9.1.100.
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Lentiviruses are a subfamily of retroviruses that are characterized by long incubation periods between infection of the host and the manifestation of clinical disease. Human immunodeficiency virus type 1, the causative agent of AIDS, is the most widely studied lentivirus. However, the lentiviruses that infect sheep, goats, and horses were identified and studied prior to the emergence of human immunodeficiency virus type 1. These and other animal lentiviruses provide important systems in which to investigate the molecular pathogenesis of this family of viruses. This review will focus on two animal lentivirus models: the ovine lentivirus visna virus; and the simian lentivirus, simian immunodeficiency virus. These animal lentiviruses have been used to examine, in particular, the pathogenesis of lentivirus-induced central nervous system disease as models for humans with AIDS as well as other chronic diseases.
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Lairmore, M. D., S. T. Butera, G. N. Callahan, and J. C. DeMartini. "Spontaneous interferon production by pulmonary leukocytes is associated with lentivirus-induced lymphoid interstitial pneumonia." Journal of Immunology 140, no. 3 (February 1, 1988): 779–85. http://dx.doi.org/10.4049/jimmunol.140.3.779.
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Abstract Ovine lentiviruses share genome sequence, structural features, and replicative mechanisms with HIV, the etiologic agent of AIDS. A lamb model of lentivirus-induced lymphoid interstitial pneumonia, comparable to lymphoid interstitial pneumonia associated with pediatric AIDS, was used to investigate production of leukocyte-soluble mediators. Lentivirus-infected lambs and adult sheep with severe lymphoid interstitial pneumonia had significantly elevated levels of spontaneous interferon (IFN) production from pulmonary leukocytes compared with ovine lentiviruses-infected animals with mild or no lesions of lymphoid interstitial pneumonia or non-infected controls. However, peripheral blood mononuclear cells from lentivirus-infected lambs did not spontaneously release significant amounts of IFN. IFN production by pulmonary lymph node lymphocytes was enhanced in the presence of lentivirus-infected alveolar macrophages. Animals with lentivirus-induced disease and spontaneous IFN production had enhanced virus replication within tissues. The ovine lentiviruses-induced IFN had a m.w. of between 25,000 and 35,000 and was resistant to freeze/thawing procedures. The IFN activity was sensitive to trypsin and stable to low pH and heat. IFN with similar physical and biochemical properties was produced when ovine lentiviruses was added to control leukocyte cultures. IL-2 and PGE2 production and responses to mitogen by pulmonary lymph node lymphocytes of lentivirus-diseased lambs were not statistically different from control animals. Increased local production of IFN in lentivirus-infected host tissues may serve to accelerate the entry of leukocytes into virus-induced lesions promoting cell-mediated tissue damage and also provide increased numbers of cells for virus replication.
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Hötzel, Isidro, and William P. Cheevers. "Conservation of Human Immunodeficiency Virus Type 1 gp120 Inner-Domain Sequences in Lentivirus and Type A and B Retrovirus Envelope Surface Glycoproteins." Journal of Virology 75, no. 4 (February 15, 2001): 2014–18. http://dx.doi.org/10.1128/jvi.75.4.2014-2018.2001.
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ABSTRACT We recently described a sequence similarity between the small ruminant lentivirus surface unit glycoprotein (SU) gp135 and the second conserved region (C2) of the primate lentivirus gp120 which indicates a structural similarity between gp135 and the inner proximal domain of the human immunodeficiency virus type 1 gp120 (I. Hötzel and W. P. Cheevers, Virus Res. 69:47–54, 2000). Here we found that the seven-amino-acid sequence of the gp120 strand β25 in the C5 region, which is also part of the inner proximal domain, was conserved in the SU of all lentiviruses in similar or identical positions relative to the carboxy terminus of SU. Sequences conforming to the gp135-gp120 consensus for β-strand 5 in the C2 region, which is antiparallel to β25, were then sought in the SU of other lentiviruses and retroviruses. Except for the feline immunodeficiency virus, sequences similar to the gp120-gp135 consensus for β5 and part of the preceding strand β4 were present in the SU of all lentiviruses. This motif was highly conserved among strains of each lentivirus and included a strictly conserved cysteine residue in β4. In addition, the β4/β5 consensus motif was also present in the conserved carboxy-terminal region of all type A and B retroviral envelope surface glycoproteins analyzed. Thus, the antiparallel β-strands 5 and 25 of gp120 form an SU surface highly conserved among the lentiviruses and at least partially conserved in the type A and B retroviral envelope glycoproteins.
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Armimi, Anastasia, Afina Firdaus Syuaib, Katherine Vanya, Marselina Irasonia Tan, Dessy Natalia, David Virya Chen, Chikako Ono, Yoshiharu Matsuura, Anita Artarini, and Ernawati Arifin Giri-Rachman. "SARS-CoV-2 Neutralization Assay System using Pseudo-lentivirus." Indonesian Biomedical Journal 15, no. 2 (April 18, 2023): 179–86. http://dx.doi.org/10.18585/inabj.v15i2.2212.
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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects humans' lower respiratory tracts and causes coronavirus disease-2019 (COVID-19). Neutralizing antibodies is one of the adaptive immune system responses that can reduce SARS-CoV-2 infection. This study aimed to develop a SARS-CoV-2 neutralization assay system using pseudo-lentivirus.METHODS: The plasmid used for pseudo-lentivirus production was characterized using restriction analysis. The gene encoding for SARS-CoV-2 spike protein was confirmed using sequencing. The transfection pseudo-lentivirus optimal condition was determined by choosing the transfection reagents and adding centrifugation step. Optimal pseudo-lentivirus infection was analysed using fluorescent assay and luciferase assay. The optimal condition of pseudo-lentivirus infection was determined by the target cell type and the number of pseudo-lentiviruses used for neutralization test. SARS-CoV-2 pseudo-lentivirus was used to detect neutralizing antibodies from serum samples.RESULTS: The plasmid used for pseudo-lentivirus production was characterized and confirmed to have no mutations. Lipofectamine 2000 reagent generated pseudo-lentivirus with a higher ability to infect target cells, as indicated by a percentage green fluorescent protein (GFP) of 12.68%. Pseudo-lentivirus centrifuged obtained more stable results in luciferase expression. Optimal pseudo-lentivirus infection conditions were obtained using puromycin-selected HEK 293T-ACE2 cells as target cells. The number of pseudo-lentiviruses used in the neutralization assay system was multiplicity of infection (MOI) 0.075. Serum A samples with a 1:10 dilution had the highest neutralizing antibody activity.CONCLUSION: This study shows that SARS-CoV-2 neutralization assay system using pseudo-lentivirus successfully detected neutralizing antibodies in human serum, which were indicated by a decrease in the percentage of pseudo-lentivirus infections.KEYWORDS: COVID-19, neutralizing antibody, neutralization assay, pseudo-lentivirus, SARS-COV-2
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Courgnaud, Valérie, Xavier Pourrut, Frédéric Bibollet-Ruche, Eitel Mpoudi-Ngole, Anke Bourgeois, Eric Delaporte, and Martine Peeters. "Characterization of a Novel Simian Immunodeficiency Virus from Guereza Colobus Monkeys (Colobus guereza) in Cameroon: a New Lineage in the Nonhuman Primate Lentivirus Family." Journal of Virology 75, no. 2 (January 15, 2001): 857–66. http://dx.doi.org/10.1128/jvi.75.2.857-866.2001.
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ABSTRACT Exploration of the diversity among primate lentiviruses is necessary to elucidate the origins and evolution of immunodeficiency viruses. During a serological survey in Cameroon, we screened 25 wild-born guereza colobus monkeys (Colobus guereza) and identified 7 with HIV/SIV cross-reactive antibodies. In this study, we describe a novel lentivirus, named SIVcol, prevalent in guereza colobus monkeys. Genetic analysis revealed that SIVcol was very distinct from all other known SIV/HIV isolates, with average amino acid identities of 40% for Gag, 50% for Pol, 28% for Env, and around 25% for proteins encoded by five other genes. Phylogenetic analyses confirmed that SIVcol is genetically distinct from other previously characterized primate lentiviruses and clusters independently, forming a novel lineage, the sixth in the current classification.Cercopithecidae monkeys (Old World monkeys) are subdivided into two subfamilies, the Colobinae and theCercopithecinae, and, so far, allCercopithecidae monkeys from which lentiviruses have been isolated belong to the Cercopithecinae subfamily. Therefore, SIVcol from guereza colobus monkeys (C. guereza) is the first primate lentivirus identified in the Colobinaesubfamily and the divergence of SIVcol may reflect divergence of the host lineage.
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Browning, Matthew T., Russell D. Schmidt, Kathy A. Lew, and Tahir A. Rizvi. "Primate and Feline Lentivirus Vector RNA Packaging and Propagation by Heterologous Lentivirus Virions." Journal of Virology 75, no. 11 (June 1, 2001): 5129–40. http://dx.doi.org/10.1128/jvi.75.11.5129-5140.2001.
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ABSTRACT Development of safe and effective gene transfer systems is critical to the success of gene therapy protocols for human diseases. Currently, several primate lentivirus-based gene transfer systems, such as those based on human and simian immunodeficiency viruses (HIV/SIV), are being tested; however, their use in humans raises safety concerns, such as the generation of replication-competent viruses through recombination with related endogenous retroviruses or retrovirus-like elements. Due to the greater phylogenetic distance from primate lentiviruses, feline immunodeficiency virus (FIV) is becoming the lentivirus of choice for human gene transfer systems. However, the safety of FIV-based vector systems has not been tested experimentally. Since lentiviruses such as HIV-1 and SIV have been shown to cross-package their RNA genomes, we tested the ability of FIV RNA to get cross-packaged into primate lentivirus particles such as HIV-1 and SIV, as well as a nonlentiviral retrovirus such as Mason-Pfizer monkey virus (MPMV), and vice versa. Our results reveal that FIV RNA can be cross-packaged by primate lentivirus particles such as HIV-1 and SIV and vice versa; however, a nonlentivirus particle such as MPMV is unable to package FIV RNA. Interestingly, FIV particles can package MPMV RNA but cannot propagate the vector RNA further for other steps of the retrovirus life cycle. These findings reveal that diverse retroviruses are functionally more similar than originally thought and suggest that upon coinfection of the same host, cross- or copackaging may allow distinct retroviruses to generate chimeric variants with unknown pathogenic potential.
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Chen, Jianbo, Douglas Powell, and Wei-Shau Hu. "High Frequency of Genetic Recombination Is a Common Feature of Primate Lentivirus Replication." Journal of Virology 80, no. 19 (October 1, 2006): 9651–58. http://dx.doi.org/10.1128/jvi.00936-06.
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ABSTRACT Recent studies indicate that human immunodeficiency virus type 1 (HIV-1) recombines at exceedingly high rates, approximately 1 order of magnitude more frequently than simple gammaretroviruses such as murine leukemia virus and spleen necrosis virus. We hypothesize that this high frequency of genetic recombination is a common feature of primate lentiviruses. Alternatively, it is possible that HIV-1 is unique among primate lentiviruses in possessing high recombination rates. Among other primate lentiviruses, only the molecular mechanisms of HIV-2 replication have been extensively studied. There are reported differences between the replication mechanisms of HIV-1 and those of HIV-2, such as preferences for RNA packaging in cis and properties of reverse transcriptase and RNase H activities. These biological disparities could lead to differences in recombination rates between the two viruses. Currently, HIV-1 is the only primate lentivirus in which recombination rates have been measured. To test our hypothesis, we established recombination systems to measure the recombination rates of two other primate lentiviruses, HIV-2 and simian immunodeficiency virus from African green monkeys (SIVagm), in one round of viral replication. We determined that, for markers separated by 588, 288, and 90 bp, HIV-2 recombined at rates of 7.4%, 5.5%, and 2.4%, respectively, whereas SIVagm recombined at rates of 7.8%, 5.6%, and 2.7%, respectively. These high recombination rates are within the same range as the previously measured HIV-1 recombination rates. Taken together, our results indicate that HIV-1, HIV-2, and SIVagm all possess high recombination frequencies; hence, the high recombination potential is most likely a common feature of primate lentivirus replication.
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Baccam, Prasith, Robert J. Thompson, Yuxing Li, Wendy O. Sparks, Michael Belshan, Karin S. Dorman, Yvonne Wannemuehler, J. Lindsay Oaks, James L. Cornette, and Susan Carpenter. "Subpopulations of Equine Infectious Anemia Virus Rev Coexist In Vivo and Differ in Phenotype." Journal of Virology 77, no. 22 (November 15, 2003): 12122–31. http://dx.doi.org/10.1128/jvi.77.22.12122-12131.2003.
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ABSTRACT Lentiviruses exist in vivo as a population of related, nonidentical genotypes, commonly referred to as quasispecies. The quasispecies structure is characteristic of complex adaptive systems and contributes to the high rate of evolution in lentiviruses that confounds efforts to develop effective vaccines and antiviral therapies. Here, we describe analyses of genetic data from longitudinal studies of genetic variation in a lentivirus regulatory protein, Rev, over the course of disease in ponies experimentally infected with equine infectious anemia virus. As observed with other lentivirus data, the Rev variants exhibited a quasispecies character. Phylogenetic and partition analyses suggested that the Rev quasispecies comprised two distinct subpopulations that coexisted during infection. One subpopulation appeared to accumulate changes in a linear, time-dependent manner, while the other evolved radially from a common variant. Over time, the two subpopulations cycled in predominance coincident with changes in the disease state, suggesting that the two groups differed in selective advantage. Transient expression assays indicated the two populations differed significantly in Rev nuclear export activity. Chimeric proviral clones containing Rev genotypes representative of each population differed in rate and overall level of virus replication in vitro. The coexistence of genetically distinct viral subpopulations that differ in phenotype provides great adaptability to environmental changes within the infected host. A quasispecies model with multiple subpopulations may provide additional insight into the nature of lentivirus reservoirs and the evolution of antigenic and drug-resistant variants.
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Narayan, O., D. Sheffer, J. E. Clements, and G. Tennekoon. "Restricted replication of lentiviruses. Visna viruses induce a unique interferon during interaction between lymphocytes and infected macrophages." Journal of Experimental Medicine 162, no. 6 (December 1, 1985): 1954–69. http://dx.doi.org/10.1084/jem.162.6.1954.
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Lentivirus infections are characterized by a persistent, restricted type of virus replication in tissues. Using sheep and goat lentiviruses, whose target cells in vivo are macrophages, we explored virus-host cell interactions to determine whether an interferon (IFN) is produced during virus replication in vivo which causes restricted replication. We show that the lentiviruses were incapable of inducing IFN directly in any infected cell, including macrophages and lymphocytes. However, after infection with these viruses, sheep and goat macrophages acquired a factor that triggered IFN production by T lymphocytes. Only sheep/goat lentiviruses were capable of inducing the factor and, although these viruses replicated productively in various cell cultures of the natural host animal, only infected macrophages developed the IFN-inducing factor. The factor was produced continuously and was strictly cell associated, requiring direct contact with lymphocytes. The lymphocytes responded with a single, sudden release of IFN beginning 7 h after cocultivation and reaching peak values at 48 h, after which they ceased production and became refractory. IFN production was not immunologically specific and did not require histocompatibility between donors of the two cell types. The IFN is a nonglycosylated protein of molecular weight 54,000-64,000, and is stable to heat and acid treatments. These findings identify a unique IFN and a new method for virus induction of IFN. The novel two-stage process of induction provides a mechanism for local amplification and continuity of production of IFN in vivo. This is compatible with infection in the animal whose lentivirus-induced pathologic lesions consist of accumulations of lymphocytes and infected macrophages in target tissues.
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Kafri, Tal, Henriette van Praag, Ling Ouyang, Fred H. Gage, and Inder M. Verma. "A Packaging Cell Line for Lentivirus Vectors." Journal of Virology 73, no. 1 (January 1, 1999): 576–84. http://dx.doi.org/10.1128/jvi.73.1.576-584.1999.
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ABSTRACT Lentivirus vectors can transduce dividing and nondividing cells. Using three-plasmid transient transfections, high-titer (>109 IU/ml) recombinant lentivirus vectors pseudotyped with vesicular stomatitis virus G (VSV-G) protein can be generated (T. Kafri et al., Nat. Genet. 17:314–317, 1997; H. Miyoshi et al., Proc. Natl. Acad. Sci. USA 94:10319–10323, 1997; L. Naldini et al., Science 272:263–267, 1996). The recombinant lentiviruses can efficiently infect brain, liver, muscle, and retinal tissue in vivo. Furthermore, the transduced tissues demonstrated long-term expression of reporter genes in immunocompetent rodents. We now report the generation of a tetracycline-inducible VSV-G pseudotyped lentivirus packaging cell line which can generate virus particles at titers greater than 106 IU/ml for at least 3 to 4 days. The vector produced by the inducible cell line can be concentrated to titers of 109 IU/ml and can efficiently transduce nondividing cells in vitro and in vivo. The availability of a lentivirus packaging cell line will significantly facilitate the production of high-titer lentivirus vectors for gene therapy and study of human immunodeficiency virus biology.
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Kania, Stephen A., Melissa A. Kennedy, and L. N. D. Potgieter. "Serologic Reactivity Using Conserved Envelope Epitopes in Feline Lentivirus-Infected Felids." Journal of Veterinary Diagnostic Investigation 9, no. 2 (April 1997): 125–29. http://dx.doi.org/10.1177/104063879700900203.
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An enzyme-linked immunosorbent assay (ELISA) based on synthetic peptides identical to lentivirus envelope protein amino acid sequences was used to study serologic reactivity of lentivirus-infected domestic cats and nondomestic felids. One feline immunodeficiency virus (FIV) peptide, P237, was consistently recognized by antibodies from FIV-infected cats, but 2 other FIV peptide antigens were not. The molecular basis for this serologic reactivity was examined. Lentivirus-infected nondomestic Felis species reacted intensely with a puma lentivirus (PLV) peptide corresponding to the conserved FIV peptide. However, lentivirus-infected Panthera species, from which a different lentivirus has been isolated, did not react with the PLV. FIV-infected domestic felids also did not have significant reactivity with the PLV peptide. The peptide ELISA is comparable in sensitivity and specificity to western blot analysis and a commercial enzyme immunoassay. Unlike the other assays, however, the peptide ELISA is inexpensive, requires a small amount of serum, enables the study of specific isotype reactivity, and discriminates between antibodies to FIV and those to PLV. Antibody tests based upon the FIV and the PLV peptides should be useful for detecting the possible introduction of FIV into exotic felids or of lentiviruses from nondomestic felids into the domestic cat population.
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St-Louis, Marie-Claude, Mihaela Cojocariu, and Denis Archambault. "The molecular biology of bovine immunodeficiency virus: a comparison with other lentiviruses." Animal Health Research Reviews 5, no. 2 (December 2004): 125–43. http://dx.doi.org/10.1079/ahr200496.
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AbstractBovine immunodeficiency virus (BIV) was first isolated in 1969 from a cow, R-29, with a wasting syndrome. The virus isolated induced the formation of syncytia in cell cultures and was structurally similar to maedi-visna virus. Twenty years later, it was demonstrated that the bovine R-29 isolate was indeed a lentivirus with striking similarity to the human immunodeficiency virus. Like other lentiviruses, BIV has a complex genomic structure characterized by the presence of several regulatory/accessory genes that encode proteins, some of which are involved in the regulation of virus gene expression. This manuscript aims to review biological and, more particularly, molecular aspects of BIV, with emphasis on regulatory/accessory viral genes/proteins, in comparison with those of other lentiviruses.
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Hatziioannou, Theodora, Simone Cowan, and Paul D. Bieniasz. "Capsid-Dependent and -Independent Postentry Restriction of Primate Lentivirus Tropism in Rodent Cells." Journal of Virology 78, no. 2 (January 15, 2004): 1006–11. http://dx.doi.org/10.1128/jvi.78.2.1006-1011.2004.
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ABSTRACT Retrovirus tropism can be restricted by cellular factors such as Fv1, Ref1, and Lv1 that inhibit infection by targeting the incoming viral capsid. Here, we show that rodent cells exhibit differential sensitivity to infection by vesicular stomatitis virus G-pseudotyped lentiviruses and that differences between human immunodeficiency virus type 1 and simian immunodeficiency virus (SIVmac) infectivity are sometimes, but not always, governed by determinants in capsid-p2. In at least one case, resistance to SIVmac infection could be eliminated by saturation of target cells with noninfectious SIVmac particles. However, cross-saturation experiments and analysis of Fv1-null cells engineered to express natural or artificial Fv1 proteins revealed that lentivirus restriction in mouse cells is independent of Fv1. Overall, these findings indicate that novel restriction factors in rodents can modulate sensitivity to specific primate lentiviruses.
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de Pablo-Maiso, Lorena, Ana Doménech, Irache Echeverría, Carmen Gómez-Arrebola, Damián de Andrés, Sergio Rosati, Esperanza Gómez-Lucia, and Ramsés Reina. "Prospects in Innate Immune Responses as Potential Control Strategies against Non-Primate Lentiviruses." Viruses 10, no. 8 (August 17, 2018): 435. http://dx.doi.org/10.3390/v10080435.
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Lentiviruses are infectious agents of a number of animal species, including sheep, goats, horses, monkeys, cows, and cats, in addition to humans. As in the human case, the host immune response fails to control the establishment of chronic persistent infection that finally leads to a specific disease development. Despite intensive research on the development of lentivirus vaccines, it is still not clear which immune responses can protect against infection. Viral mutations resulting in escape from T-cell or antibody-mediated responses are the basis of the immune failure to control the infection. The innate immune response provides the first line of defense against viral infections in an antigen-independent manner. Antiviral innate responses are conducted by dendritic cells, macrophages, and natural killer cells, often targeted by lentiviruses, and intrinsic antiviral mechanisms exerted by all cells. Intrinsic responses depend on the recognition of the viral pathogen-associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs), and the signaling cascades leading to an antiviral state by inducing the expression of antiviral proteins, including restriction factors. This review describes the latest advances on innate immunity related to the infection by animal lentiviruses, centered on small ruminant lentiviruses (SRLV), equine infectious anemia virus (EIAV), and feline (FIV) and bovine immunodeficiency viruses (BIV), specifically focusing on the antiviral role of the major restriction factors described thus far.
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van der Loo, W., J. Abrantes, and P. J. Esteves. "Sharing of Endogenous Lentiviral Gene Fragments among Leporid Lineages Separated for More than 12 Million Years." Journal of Virology 83, no. 5 (December 24, 2008): 2386–88. http://dx.doi.org/10.1128/jvi.01116-08.
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ABSTRACT Lentiviruses are causal agents of severe pathologies of a variety of mammals, including cattle and humans (e.g., AIDS and different types of lymphoma). While endogenous forms of lentivirus do not occur in these species, A. Katzourakis and coworkers (A. Katzourakis, M. Tristem, O. G. Pybus, and R. J. Gifford, Proc. Natl. Acad. Sci. USA 104:6261-6265, 2007) recently reported the presence in the genome of the European rabbit (Oryctolagus cuniculus) of multiple sequences defining a lentiviral subgroup elegantly referred to as RELIK (rabbit endogenous lentivirus type K). Sequence comparisons indicated that the RELIK ancestor may have integrated into the rabbit lineage more than 7 million years ago. We have substantiated this by producing sequence data certifying the sharing of RELIK sequences among leporid lineages that diverged some 12 million years ago.
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Han, Guan-Zhu, and Michael Worobey. "A Primitive Endogenous Lentivirus in a Colugo: Insights into the Early Evolution of Lentiviruses." Molecular Biology and Evolution 32, no. 1 (October 27, 2014): 211–15. http://dx.doi.org/10.1093/molbev/msu297.
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Johnston, J. B., Y. Jiang, G. van Marle, M. B. Mayne, W. Ni, J. Holden, J. C. McArthur, and C. Power. "Lentivirus Infection in the Brain Induces Matrix Metalloproteinase Expression: Role of Envelope Diversity." Journal of Virology 74, no. 16 (August 15, 2000): 7211–20. http://dx.doi.org/10.1128/jvi.74.16.7211-7220.2000.
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ABSTRACT Infection of the brain by lentiviruses, including human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV), causes inflammation and results in neurodegeneration. Molecular diversity within the lentivirus envelope gene has been implicated in the regulation of cell tropism and the host response to infection. Here, we examine the hypothesis that envelope sequence diversity modulates the expression of host molecules implicated in lentivirus-induced brain disease, including matrix metalloproteinases (MMP) and related transcription factors. Infection of primary macrophages by chimeric HIV clones containing brain-derived envelope fragments from patients with HIV-associated dementia (HAD) or nondemented AIDS patients (HIV-ND) showed that MMP-2 and -9 levels in conditioned media were significantly higher for the HAD clones. Similarly, STAT-1 and JAK-1 levels were higher in macrophages infected by HAD clones. Infections of primary feline macrophages by the neurovirulent FIV strain (V1CSF), the less neurovirulent strain (Petaluma), and a chimera containing the V1CSF envelope in a Petaluma background (FIV-Ch) revealed that MMP-2 and -9 levels were significantly higher in conditioned media from V1CSF- and FIV-Ch-infected macrophages, which was associated with increased intracellular STAT-1 and JAK-1 levels. The STAT-1 inhibitor fludarabine significantly reduced MMP-2 expression, but not MMP-9 expression, in FIV-infected macrophages. Analysis of MMP mRNA and protein levels in brain samples from HIV-infected persons or FIV-infected cats showed that MMP-2 and -9 levels were significantly increased in lentivirus-infected brains compared to those of uninfected controls. Elevated MMP expression was accompanied by significant increases in STAT-1 and JAK-1 mRNA and protein levels in the same brain samples. The present findings indicate that two lentiviruses, HIV and FIV, have common mechanisms of MMP-2 and -9 induction, which is modulated in part by envelope sequence diversity and the STAT-1/JAK-1 signaling pathway.
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Abergel, Chantal, David L. Robertson, and Jean-Michel Claverie. "“Hidden” dUTPase Sequence in Human Immunodeficiency Virus Type 1 gp120." Journal of Virology 73, no. 1 (January 1, 1999): 751–53. http://dx.doi.org/10.1128/jvi.73.1.751-753.1999.
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ABSTRACT A coding region homologous to the sequence for essential eukaryotic enzyme dUTPase has been identified in different genomic regions of several viral lineages. Unlike the nonprimate lentiviruses (caprine arthritis- encephalitis virus, equine infectious anemia virus, feline immunodeficiency virus, and visna virus), where dUTPase is integrated into the pol coding region, this enzyme has never been demonstrated to be present in the primate lentivirus genomes (human immunodeficiency virus type 1 [HIV-1], HIV-2, or the related simian immunodeficiency virus). A novel approach allowed us to identify a weak but significant sequence similarity between HIV-1 gp120 and the human dUTPase. This finding was then extended to all of the primate lentivirus lineages. Together with the recently reported fragmentary structural similarity between the V3 loop region and the Escherichia coli dUTPase (P. D. Kwong, R. Wyatt, J. Robinson, R. W. Sweet, J. Sodroski, and W. A. Hendrickson, Nature 393:648–659, 1998), our results strongly suggest that an ancestral dUTPase gene has evolved into the present primate lentivirus CD4 and cytokine receptor interacting region of gp120.
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Hayes, Kathleen A., Sadi Köksoy, Andrew J. Phipps, Wayne R. Buck, Gary J. Kociba, and Lawrence E. Mathes. "Lentivirus-Specific Cytotoxic T-Lymphocyte Responses Are Rapidly Lost in Thymectomized Cats Infected with Feline Immunodeficiency Virus." Journal of Virology 79, no. 13 (July 1, 2005): 8237–42. http://dx.doi.org/10.1128/jvi.79.13.8237-8242.2005.
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ABSTRACT To what extent the thymus is needed to preserve the virus-specific cytotoxic T-lymphocyte (CTL) response of lentivirus-infected adults is unclear. Presented here is the first definitive study using thymectomized (ThX) animals to directly evaluate the contribution of thymic function to lentivirus-specific CTL response and the control of lentivirus infections. ThX and mock-ThX cats were inoculated with feline immunodeficiency virus (FIV) and monitored for their FIV-specific CTL responses. Early in infection, both FIV-ThX and FIV-mock-ThX cats produced similar CTL responses, but surprisingly, after 20 weeks, the FIV-ThX cats showed a statistically significant loss of FIV-specific CTL activity, while FIV-infected cats with intact thymuses continued to maintain FIV-specific CTL. The loss of CTL did not affect plasma virus load, which remained elevated for both groups. These results emphasize the importance of thymic integrity in maintaining immunity to lentiviruses, but also bring into question the notion that virus load is regulated predominantly by the virus-specific CTL response.
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Rosati, Sergio, Jimmy Kwang, and James E. Keen. "Genome Analysis of North American Small Ruminant Lentiviruses by Polymerase Chain Reaction and Restriction Enzyme Analysis." Journal of Veterinary Diagnostic Investigation 7, no. 4 (October 1995): 437–43. http://dx.doi.org/10.1177/104063879500700403.
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The polymerase chain reaction (PCR) was used to amplify portions of the gag and env structural genes of 8 ovine and 1 caprine lentivirus isolates of North American origin. Three sets of primers were used to amplify p16, p25, and Nî-gp40 gene fragments, and 1 set, annealing highly conserved portions of long terminal repeat (LTR) among small ruminant lentiviruses, was used as a positive control. Variable PCR amplification efficiency was observed. Different stringency conditions of hybridization with specific DNA probes were used to maximize detection of the PCR product. The p25 primers detected all strains, the gp40 primers detected 1 ovine and the caprine strain, and the p16 primers detected only 1 ovine isolate. All strains were detected by LTR primers. Restriction endonuclease analysis of 5 amplified p25 and 2 Nî-gp40 gene fragments revealed extensive heterogeneity among these North American small ruminant lentiviruses.
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Nogarol, Chiara, Luigi Bertolotti, Siv Klevar, Margherita Profiti, Britt Gjerset, and Sergio Rosati. "Serological characterization of small ruminant lentiviruses: A complete tool for serotyping lentivirus infection in goat." Small Ruminant Research 176 (July 2019): 42–46. http://dx.doi.org/10.1016/j.smallrumres.2019.05.010.
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Querat, G., G. Audoly, P. Sonigo, and R. Vigne. "Nucleotide sequence analysis of SA-OMVV, a visna-related ovine lentivirus: phylogenetic history of lentiviruses." Virology 175, no. 2 (April 1990): 434–47. http://dx.doi.org/10.1016/0042-6822(90)90428-t.
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Langley, Raymond J., Vanessa M. Hirsch, Stephen J. O'Brien, Diane Adger-Johnson, Robert M. Goeken, and Robert A. Olmsted. "Nucleotide Sequence Analysis of Puma Lentivirus (PLV-14): Genomic Organization and Relationship to Other Lentiviruses." Virology 202, no. 2 (August 1994): 853–64. http://dx.doi.org/10.1006/viro.1994.1407.
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Da Silva Teixeira, Maria Fatima, Véronique Lambert, Laila Mselli-Lakahl, Abdelkamel Chettab, Yahia Chebloune, and Jean-François Mornex. "Immortalization of caprine fibroblasts permissive for replication of small ruminant lentiviruses." American Journal of Veterinary Research 58, no. 6 (June 1, 1997): 579–84. http://dx.doi.org/10.2460/ajvr.1997.58.06.579.
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Abstract Objective To establish immortalized caprine fibroblastic cell lines permissive for replication of small ruminant lentiviruses. Animals Carpal synovial membrane explants collected aseptically from a surgically delivered fetus of a lentivirus-seronegative goat. Procedure Immortalization of goat embryonic fibroblasts was performed by DNA transfection with plasmids coding for simian virus 40 large T antigen. The generated cell lines were phenotypically characterized. Cytogenetics, growth pattern, and sensitivity to viral infection were studied. Results 3 cell lines, designated TIGEF, mMTSV-54, and mMTSV-93, were generated. They had a more rapid doubling time than did fibroblasts from which they were derived, and retained morphologic and phenotypic fibroblastic characteristics. They were immortalized but not transformed because tumor formation was not promoted after their SC injection into athymic nude mice. The 3 cell lines were susceptible to caprine arthritisencephalitis virus and visna-maedi virus infections, and supported a complete virus replication cycle. Conclusions Cultured caprine fibroblastic cells were immortalized, using simian virus 40 large T antigen. The TIGEF, mMTSV-54, and mMTSV-93 immortalized cell lines were permissive to in vitro small ruminant lentivirus replication. Clinical Relevance Because lentivirus detection, as well as detailed studies of host-lentivirus interactions, are hampered by differences in viral susceptibility of each primary culture, permanent cell lines are essential tools for such analysis. (Am J Vet Res 1997;58:579–584)
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Berkowitz, Robert, Heini Ilves, Wei Yu Lin, Karl Eckert, Andrea Coward, Stan Tamaki, Gabor Veres, and Ivan Plavec. "Construction and Molecular Analysis of Gene Transfer Systems Derived from Bovine Immunodeficiency Virus." Journal of Virology 75, no. 7 (April 1, 2001): 3371–82. http://dx.doi.org/10.1128/jvi.75.7.3371-3382.2001.
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ABSTRACT Because lentiviruses are able to infect nondividing cells, these viruses might be utilized in gene therapy applications where the target cell does not divide. However, it has been suggested that the introduction of primate lentivirus sequences, particularly those of human immunodeficiency virus, into human cells may pose a health risk for the patient. To avoid this concern, we have constructed gene transfer systems based on a nonprimate lentivirus, bovine immunodeficiency virus. A panel of vectors and packaging constructs was generated and analyzed in a transient expression system for virion production and maturation, vector expression and encapsidation, and envelope protein pseudotyping. Virion preparations were also analyzed for transduction efficiency in a panel of human and nonhuman primary cells and immortalized cell lines. The virion preparations transduced most of the target cell types, with efficiencies up to 90% and with titers of unconcentrated virus up to 5 × 105infectious doses/ml. In addition, infection of nondividing human cells, including unstimulated hematopoietic stem cells and irradiated endothelial cells, was observed.
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TerWee, Julie A., Jennifer K. Yactor, Kerry S. Sondgeroth, and Sue VandeWoude. "Puma Lentivirus Is Controlled in Domestic Cats after Mucosal Exposure in the Absence of Conventional Indicators of Immunity." Journal of Virology 79, no. 5 (March 1, 2005): 2797–806. http://dx.doi.org/10.1128/jvi.79.5.2797-2806.2005.
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ABSTRACT A high percentage of free-ranging pumas (Felis concolor) are infected with feline lentiviruses (puma lentivirus, feline immunodeficiency virus Pco [FIV-Pco], referred to here as PLV) without evidence of disease. PLV establishes productive infection in domestic cats following parenteral exposure but, in contrast to domestic cat FIV, it does not cause T-cell dysregulation. Here we report that cats exposed to PLV oro-nasally became infected yet rapidly cleared peripheral blood mononuclear cell (PBMC) proviral load in the absence of a correlative specific immune response. Two groups of four specific-pathogen-free cats were exposed to PLV via the mucosal (oro-nasal) or parenteral (i.v.) route. All animals were PBMC culture positive and PCR positive within 3 weeks postinfection and seroconverted without exhibiting clinical disease; however, three or four oro-nasally infected animals cleared circulating proviral DNA within 3 months. Antibody titers reached higher levels in animals that remained persistently infected. PLV antigen-induced proliferation was slightly greater in mucosally inoculated animals, but no differences were noted in cytotoxic T-lymphocyte responses or cytokine profiles between groups. The distribution of virus was predominantly gastrointestinal as opposed to lymphoid in all animals in which virus was detected at necropsy. Possible mechanisms for viral clearance include differences in viral fitness required for crossing mucosal surfaces, a threshold dose requirement for persistence, or an undetected sterilizing host immune response. This is the first report of control of a productive feline or primate lentivirus infection in postnatally exposed, seropositive animals. Mechanisms underlying this observation will provide clues to containment of immunodeficiency disease and could prompt reexamination of vaccine-induced immunity against human immunodeficiency virus and other lentiviruses.
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Buchschacher, Gary L., and Flossie Wong-Staal. "Development of lentiviral vectors for gene therapy for human diseases." Blood 95, no. 8 (April 15, 2000): 2499–504. http://dx.doi.org/10.1182/blood.v95.8.2499.
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Abstract Retroviral vectors derived from murine retroviruses are being used in several clinical gene therapy trials. Recently, progress has been made in the development of vectors based on the lentivirus genus of retroviruses, which ironically includes a major human pathogen, human immunodeficiency virus (HIV). As these vector systems for clinical gene transfer are developed, it is important to understand the rationale behind their design and development. This article reviews the fundamental features of retrovirus replication and of the elements necessary for development of a retroviral vector system, and it discusses why vector systems based on HIV or other lentiviruses have the potential to become important tools in clinical gene therapy.
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Buchschacher, Gary L., and Flossie Wong-Staal. "Development of lentiviral vectors for gene therapy for human diseases." Blood 95, no. 8 (April 15, 2000): 2499–504. http://dx.doi.org/10.1182/blood.v95.8.2499.008k35_2499_2504.
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Retroviral vectors derived from murine retroviruses are being used in several clinical gene therapy trials. Recently, progress has been made in the development of vectors based on the lentivirus genus of retroviruses, which ironically includes a major human pathogen, human immunodeficiency virus (HIV). As these vector systems for clinical gene transfer are developed, it is important to understand the rationale behind their design and development. This article reviews the fundamental features of retrovirus replication and of the elements necessary for development of a retroviral vector system, and it discusses why vector systems based on HIV or other lentiviruses have the potential to become important tools in clinical gene therapy.
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Kang, Yubin, Christopher J. Moressi, Todd E. Scheetz, Litao Xie, Diane Thi Tran, Thomas L. Casavant, Prashanth Ak, Craig J. Benham, Beverly L. Davidson, and Paul B. McCray. "Integration Site Choice of a Feline Immunodeficiency Virus Vector." Journal of Virology 80, no. 17 (September 1, 2006): 8820–23. http://dx.doi.org/10.1128/jvi.00719-06.
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ABSTRACT We mapped 226 unique integration sites in human hepatoma cells following gene transfer with a feline immunodeficiency virus (FIV)-based lentivirus vector. FIV integrated across the entire length of the transcriptional units. Microarray data indicated that FIV integration favored actively transcribed genes. Approximately 21% of FIV integrations within transcriptional units occurred in genes regulated by the LEDGF/p75 transcriptional coactivator. DNA in regions of FIV insertion sites exhibited a “bendable” structure and a pattern of duplex destabilization favoring strand separation. FIV integration preferences are more similar to those of primate lentiviruses and distinct from those of Moloney murine leukemia virus, avian sarcoma leukosis virus, and foamy virus.
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Franklin, S. P., J. L. Troyer, J. A. Terwee, L. M. Lyren, W. M. Boyce, S. P. D. Riley, M. E. Roelke, K. R. Crooks, and S. VandeWoude. "Frequent Transmission of Immunodeficiency Viruses among Bobcats and Pumas." Journal of Virology 81, no. 20 (August 1, 2007): 10961–69. http://dx.doi.org/10.1128/jvi.00997-07.
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ABSTRACT With the exception of human immunodeficiency virus (HIV), which emerged in humans after cross-species transmissions of simian immunodeficiency viruses from nonhuman primates, immunodeficiency viruses of the family Lentiviridae represent species-specific viruses that rarely cross species barriers to infect new hosts. Among the Felidae, numerous immunodeficiency-like lentiviruses have been documented, but only a few cross-species transmissions have been recorded, and these have not been perpetuated in the recipient species. Lentivirus seroprevalence was determined for 79 bobcats (Lynx rufus) and 31 pumas (Puma concolor) from well-defined populations in Southern California. Partial genomic sequences were subsequently obtained from 18 and 12 seropositive bobcats and pumas, respectively. Genotypes were analyzed for phylogenic relatedness and genotypic composition among the study set and archived feline lentivirus sequences. This investigation of feline immunodeficiency virus infection in bobcats and pumas of Southern California provides evidence that cross-species infection has occurred frequently among these animals. The data suggest that transmission has occurred in multiple locations and are most consistent with the spread of the virus from bobcats to pumas. Although the ultimate causes remain unknown, these transmission events may occur as a result of puma predation on bobcats, a situation similar to that which fostered transmission of HIV to humans, and likely represent the emergence of a lentivirus with relaxed barriers to cross-species transmission. This unusual observation provides a valuable opportunity to evaluate the ecological, behavioral, and molecular conditions that favor repeated transmissions and persistence of lentivirus between species.
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Poeschla, Eric M., and David J. Looney. "CXCR4 Is Required by a Nonprimate Lentivirus: Heterologous Expression of Feline Immunodeficiency Virus in Human, Rodent, and Feline Cells." Journal of Virology 72, no. 8 (August 1, 1998): 6858–66. http://dx.doi.org/10.1128/jvi.72.8.6858-6866.1998.
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ABSTRACT A heterologous feline immunodeficiency virus (FIV) expression system permitted high-level expression of FIV proteins and efficient production of infectious FIV in human cells. These results identify the FIV U3 element as the sole restriction to the productive phase of replication in nonfeline cells. Heterologous FIV expression in a variety of human cell lines resulted in profuse syncytial lysis that was FIV env specific, CD4 independent, and restricted to cells that express CXCR4, the coreceptor for T-cell-line-adapted strains of human immunodeficiency virus. Stable expression of human CXCR4 in CXCR4-negative human and rodent cell lines resulted in extensive FIV Env-mediated, CXCR4-dependent cell fusion and infection. In feline cells, stable overexpression of human CXCR4 resulted in increased FIV infectivity and marked syncytium formation during FIV replication or after infection with FIV Env-expressing vectors. The use of CXCR4 is a fundamental feature of lentivirus biology independent of CD4 and a shared cellular link to infection and cytopathicity for distantly related lentiviruses that cause AIDS. Their conserved use implicates chemokine receptors as primordial lentivirus receptors.
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Soares, Rafael Rodrigues, Francisco Alberto Moraes Viana Júnior, Diego Moraes Soares, Thais Bastos Rocha, Leandro Henrique Veiga de Sousa, Hamilton Pereira Santos, and Helder de Moraes Pereira. "Serological evidence and spatial analysis of small ruminant lentiviruses in herds in Maranhão, Brazil." Acta Veterinaria Brasilica 14, no. 4 (December 29, 2020): 244–51. http://dx.doi.org/10.21708/avb.2020.14.4.9001.
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Caprine arthritis encephalitis and Maedi-Visnaare lentiviruses affecting goats and sheep, respectively. Despite the literature having studies about these diseases, there is a constant demand and the need to study the health status of flocks that exploit economically. Therefore, this study aimed to assess the frequency of small ruminant lentiviruses explored in regional locations of Chapadinha and Itapecuru Mirim, that compose the microregion of Low Parnaíba, Maranhão, Brazil, as well as analyze the spatial distribution of outbreaks in the studied regions. Therefore, 241 properties were visited, where blood was collected in 1150 sheep and 1260 goats and tested by agar gel immunodiffusion (AGID). Epidemiological questionnaire was applied and collected the geographic coordinates. There was a low frequencyfor lentivirus, with 0.39% (5/1260) of goats and 0.08% (1/1150) of sheep. Regarding the spatial analysis, the reagent flocks were distributed in strategic cities for commercialization throughout the microregion. There was a low occurrence of lentiviruses.The municipalities of Cantanhede and Pirapemas of the regional of Itapecuru Mirimand Brejo and Magalhães de Almeida had reagent flocks for CAE. Whereas the municipality of Matões do Norte presented flock reagent to Maedi-Visna, this belonging to the regional of Chapadinha.
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Benveniste, R. E., L. O. Arthur, C. C. Tsai, R. Sowder, T. D. Copeland, L. E. Henderson, and S. Oroszlan. "Isolation of a lentivirus from a macaque with lymphoma: comparison with HTLV-III/LAV and other lentiviruses." Journal of Virology 60, no. 2 (1986): 483–90. http://dx.doi.org/10.1128/jvi.60.2.483-490.1986.
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Jin, Jing, Timothy Sturgeon, Chaoping Chen, Simon C. Watkins, Ora A. Weisz, and Ronald C. Montelaro. "Distinct Intracellular Trafficking of Equine Infectious Anemia Virus and Human Immunodeficiency Virus Type 1 Gag during Viral Assembly and Budding Revealed by Bimolecular Fluorescence Complementation Assays." Journal of Virology 81, no. 20 (August 8, 2007): 11226–35. http://dx.doi.org/10.1128/jvi.00431-07.
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ABSTRACT Retroviral Gag polyproteins are necessary and sufficient for virus budding. Numerous studies of human immunodeficiency virus type 1 (HIV-1) Gag assembly and budding mechanisms have been reported, but relatively little is known about these fundamental pathways among animal lentiviruses. While there may be a general assumption that lentiviruses share common assembly mechanisms, studies of equine infectious anemia virus (EIAV) have indicated alternative cellular pathways and cofactors employed among lentiviruses for assembly and budding. In the current study, we used bimolecular fluorescence complementation to characterize and compare assembly sites and budding efficiencies of EIAV and HIV-1 Gag in both human and rodent cells. The results of these studies demonstrated that replacing the natural RNA nuclear export element (Rev-response element [RRE]) used by HIV-1 and EIAV with the hepatitis B virus posttranscriptional regulatory element (PRE) altered HIV-1, but not EIAV, Gag assembly sites and budding efficiency in human cells. Consistent with this novel observation, different assembly sites were revealed in human cells for Rev-dependent EIAV and HIV-1 Gag polyproteins. In rodent cells, Rev-dependent HIV-1 Gag assembly and budding were blocked, but changing RRE to PRE rescued HIV-1 Gag assembly and budding. In contrast, EIAV Gag polyproteins synthesized from mRNA exported via either Rev-dependent or PRE-dependent mechanisms were able to assemble and bud efficiently in rodent cells. Taken together, our results suggest that lentivirus assembly and budding are regulated by the RNA nuclear export pathway and that alternative cellular pathways can be adapted for lentiviral Gag assembly and budding.
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Sutton, Richard E., Henry T. M. Wu, Richard Rigg, Ernst Böhnlein, and Patrick O. Brown. "Human Immunodeficiency Virus Type 1 Vectors Efficiently Transduce Human Hematopoietic Stem Cells." Journal of Virology 72, no. 7 (July 1, 1998): 5781–88. http://dx.doi.org/10.1128/jvi.72.7.5781-5788.1998.
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ABSTRACT Lentiviruses are potentially advantageous compared to oncoretroviruses as gene transfer agents because they can infect nondividing cells. We demonstrate here that human immunodeficiency virus type 1 (HIV-1)-based vectors were highly efficient in transducing purified human hematopoietic stem cells. Transduction rates, measured by marker gene expression or by PCR of the integrated provirus, exceeded 50%, and transduction appeared to be independent of mitosis. Derivatives of HIV-1 were constructed to optimize the vector, and a deletion of most of Vif and Vpr was required to ensure the long-term persistence of transduced cells with relatively stable expression of the marker gene product. These results extend the utility of this lentivirus vector system.
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Yang, S. Y., P. C. Cheng, and A. W. S. Chan. "6 LENTIVIRAL TRANSGENESIS IN MICE AND NONHUMAN PRIMATES." Reproduction, Fertility and Development 20, no. 1 (2008): 83. http://dx.doi.org/10.1071/rdv20n1ab6.
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Transgenic technology is a powerful tool for investigating gene function and regulation in species ranging from fly to higher primates. The role of transgenic animal modeling has become more prominent in biomedical research; therefore, a highly efficient method for producing transgenic animals is critical for the advancement of animal modeling of genetic disorders, especially in species with limited access such as nonhuman primates. Lentiviral transgenesis is one of most efficient methods in generating transgenic animals, and has been applied in different species including mice, rats, pigs, and cattle. Here we evaluated lentiviral transgenesis by an in-depth investigation on the effect of gene construct and the method of viral delivery in mice; thus the prospect of creating transgenic nonhuman primates can be assessed. Lentiviruses carrying 25 different gene constructs in the same viral backbone were created and microinjected into the cytoplasm or the perivitelline space (PVS) of mouse zygotes; these zygotes were then compared to those subjected to the traditional pronuclear injection (PI) method. Embryo development was not affected by PVS, whereas intracytoplasmic injection produced a mild effect on embryo development, which was dependent on the manipulation skill. We found that intracytoplasmic injection of lentivirus had the highest transgenic rate (weaned pups) of approximately 54.22% (199/367), whereas the transgenic rate using PVS injection was 40.74% (22/54). However, the transgenic rate of PI was only 9.09% (4/44), which was significantly lower than the other two methods. Germline transmission was confirmed in over 90% of the transgenic lines produced by lentiviral gene transfer. In addition to the effect due to gene delivery method, variations in gene transfer efficiency were also observed when lentiviruses with different constructs were used. Our interest was to translate the lentiviral gene transfer technique into nonhuman primates for the development of a model for human disease. We evaluated the in vitro developmental rate of Rhesus macaques embryos that were microinjected into the PVS with lentiviruses carrying mutant genes leading to neurodegenerative diseases. The blastocyst rate of the lentivirus injection group (26%; 62/238) was not different from that of the control (25%; 13/52), which was without lentivirus injection. This indicates the feasibility of applying the lentiviral gene transfer technique to nonhuman primates. We carried out embryo transfers to surrogate female monkeys; however, the confirmation of pregnancy and the success of a developing nonhuman primate model of human disease were not available at the time of this writing. Here we demonstrate that lentiviral transgensis by cytoplasmic injection or PVS injection is a promising method to generate transgenic animals at high efficiency, and is superior to the traditional methods. Thus the production of a nonhuman primate model of human genetic diseases is foreseeable, and will have a significant impact on transgenic animal modeling as well as the advancement of biomedicine. This work was supported by the NCRR/NIH.
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Morin, Thierry, François Guiguen, Baya Amel Bouzar, Stéphanie Villet, Timothy Greenland, Délphine Grezel, Françoise Gounel, et al. "Clearance of a Productive Lentivirus Infection in Calves Experimentally Inoculated with Caprine Arthritis-Encephalitis Virus." Journal of Virology 77, no. 11 (June 1, 2003): 6430–37. http://dx.doi.org/10.1128/jvi.77.11.6430-6437.2003.
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ABSTRACT Lentiviruses have long been considered host-specific pathogens, but several recent observations demonstrated their capacity to conquer new hosts from different species, genera, and families. From these cross-species infections emerged new animal and human infectious diseases. The successful colonization and adaptation of a lentivirus to a nonnatural host depends on unspecific and specific host barriers. Some of those barriers exert a relative control of viral replication (i.e., cytotoxic T-lymphocyte response, viral inhibitory factors), but none of them was found able to totally clear the infection once the retrovirus is fully adapted in its host. In this study we examined the evolution of the host-lentivirus interactions occurring in an experimental animal model of cross-species infection in order to analyze the efficiency of those barriers in preventing the establishment of a persistent infection. Five newborn calves were inoculated with caprine arthritis-encephalitis virus (CAEV), and the evolution of infection was studied for more than 12 months. All the animals seroconverted in the first 0.75 to 1 month following the inoculation and remained seropositive for the remaining time of the experiment. Viral infection was productive during 4 months with isolation of replication competent virus from the blood cells and organs of the early euthanized animals. After 4 months of infection, neither replication-competent virus nor virus genome could be detected in blood cells or in the classical target organs, even after an experimental immunosuppression. No evidence of in vitro restriction of CAEV replication was observed in cells from tissues explanted from organs of these calves. These data provide the demonstration of a natural clearance of lentivirus infection following experimental inoculation of a nonnatural host, enabling perspectives of development of new potential vaccine strategies to fight against lentivirus infections.
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Mikami, Maya, and Jay Yang. "Short Hairpin RNA–mediated Selective Knockdown of NaV1.8 Tetrodotoxin-resistant Voltage-gated Sodium Channel in Dorsal Root Ganglion Neurons." Anesthesiology 103, no. 4 (October 1, 2005): 828–36. http://dx.doi.org/10.1097/00000542-200510000-00022.
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Background Voltage-gated sodium channels comprise a family of closely related proteins, each subserving different physiologic and pathologic functions. NaV1.8 is an isoform of voltage-gated sodium channel implicated in the pathogenesis of inflammatory and neuropathic pain, but currently, there is no isoform-specific inhibitor of any voltage-gated sodium channels. The authors explored the possibility of short hairpin RNA-mediated selective knockdown of NaV1.8 expression. Methods DNA constructs designed to transcribe short hairpin RNA targeting NaV1.8 were created and incorporated into recombinant lentiviruses. The virus-induced selective knockdown of NaV1.8 was examined at the protein, messenger RNA, and functional levels using Western blot, immunohistochemistry, reverse-transcription polymerase chain reaction, and patch clamp electrophysiology. Results Transduction of HEK293 cells stably expressing NaV1.8 or primary dorsal root ganglion neurons with lentivirus expressing short hairpin RNA resulted in the knockdown of NaV1.8 protein and messenger RNA concentrations. Whole cell patch clamp recordings confirmed decrease in the NaV1.8-mediated current density without changes in other biophysical properties. Conclusions A selective knockdown of NaV1.8 expression in dorsal root ganglion neurons can be attained by short hairpin RNA delivered with lentivirus. This method may provide a new gene therapy approach to controlling neuronal hyperexcitability and pathologic pain.
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Heeney, Jonathan L., Erik Rutjens, Ernst J. Verschoor, Henk Niphuis, Peter ten Haaft, Scott Rouse, Hazel McClure, et al. "Transmission of Simian Immunodeficiency Virus SIVcpz and the Evolution of Infection in the Presence and Absence of Concurrent Human Immunodeficiency Virus Type 1 Infection in Chimpanzees." Journal of Virology 80, no. 14 (July 15, 2006): 7208–18. http://dx.doi.org/10.1128/jvi.00382-06.
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ABSTRACT Current data suggest that the human immunodeficiency virus type 1 (HIV-1) epidemic arose by transmission of simian immunodeficiency virus (SIV) SIVcpz from a subspecies of common chimpanzees (Pan troglodytes troglodytes) to humans. SIVcpz of chimpanzees is itself a molecular chimera of SIVs from two or more different monkey species, suggesting that recombination was made possible by coinfection of one individual animal with different lentiviruses. However, very little is known about SIVcpz transmission and the susceptibility to lentivirus coinfection of its natural host, the chimpanzee. Here, it is revealed that either infected plasma or peripheral blood mononuclear cells readily confer infection when exposure occurs by the intravenous or mucosal route. Importantly, the presence of preexisting HIV-1 infection did not modify the kinetics of SIVcpz infection once it was established by different routes. Although humoral responses appeared as early as 4 weeks postinfection, neutralization to SIVcpz-ANT varied markedly between animals. Analysis of the SIVcpz env sequence over time revealed the emergence of genetic viral variants and persistent SIVcpz RNA levels of between 104 and 105 copies/ml plasma regardless of the presence or absence of concurrent HIV-1 infection. These unique data provide important insight into possible routes of transmission, the kinetics of acute SIVcpz infection, and how readily coinfection with SIVcpz and other lentiviruses may be established as necessary preconditions for potential recombination.
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Mellor, Andrew, Lei Huang, Lingqian Li, Henrique Lemos, Gabriela Pacholczyk, and William King. "Pivotal pathways that control host responses to lentivirus infection. (VIR7P.1053)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 208.5. http://dx.doi.org/10.4049/jimmunol.192.supp.208.5.
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Abstract Lentiviruses such as Human Immunodeficiency Virus establish persistent infections but it is unclear how lentiviruses evade host immunity. To elucidate pivotal pathways driving tolerogenic host responses to lentiviral infection we used the murine leukemia virus (LP-BM5) infection model, which causes persistent infections leading to splenomegaly, immunosuppression, and increased risk of leukemia. LP-BM5 infection induced indoleamine 2,3 dioxygenase (IDO) enzyme activity in a subset of dendritic cells expressing the B cell marker CD19 that regulate T cells. Different mouse strains exhibit variable resistance to LP-BM5 infection but all mice succumb to persistent LP-BM5 infection. In contrast, mice with genetically-induced, functional defects in Foxp3-lineage regulatory CD4 T cells (Tregs) cleared LP-BM5 infections ~4-6 weeks post infection. LP-BM5 clearance did not occur unless mice were homozygous for defective Foxp3 alleles, indicating that wild-type Tregs mediate dominant tolerogenic responses to LP-BM5 infection. Depleting CD8 T cells prevented LP-BM5 clearance in Treg defective mice, and LP-BM5 resistance correlated with diminished IDO induction, suggesting that Tregs block CD8 T cells via IDO to promote virus persistence. Thus Tregs are pivotal in promoting tolerogenic responses to LP-BM5 infection, and interfering with pathways that activate Tregs and mediate responses to activated Tregs may enhance host resistance to lentivirus infections.
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Brandin, Eleonor, Rigmor Thorstensson, Sebastian Bonhoeffer, and Jan Albert. "Rapid Viral Decay in Simian Immunodeficiency Virus-Infected Macaques Receiving Quadruple Antiretroviral Therapy." Journal of Virology 80, no. 19 (October 1, 2006): 9861–64. http://dx.doi.org/10.1128/jvi.00394-06.
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ABSTRACT The viral dynamics in human immunodeficiency virus type 1 (HIV-1) infection have been studied extensively using mathematical modeling, but data from other primate lentivirus systems are scarce. This study was initiated to increase the understanding of the differences and similarities between the different primate lentiviruses. Four cynomolgus macaques were infected with SIVmac251. Six months after infection the monkeys received a 7-day course of subcutaneous, quadruple antiretroviral therapy with zidovudine, lamivudine, tenofovir, and ritonavir-boosted lopinavir. Plasma virus levels were determined before therapy, daily during the first 10 days of therapy, and after 14 days using a sensitive commercial reverse transcriptase assay. All four monkeys showed a rapid and uniform decline in plasma virus load between day 1 and day 4 of treatment (first-phase decay). Two mathematical models, a piecewise linear regression analysis and a nonlinear model, were used to estimate the rate of viral decay in plasma and gave similar results. The mean half-life for plasma virus was 0.47 days (range, 0.37 to 0.50) and reflects the underlying decline of virus-producing CD4+ lymphocytes. This is the fastest primate lentivirus decay described hitherto. The rapid decay may be due to the high antiviral potency of the therapy or to intrinsic differences between simian immunodeficiency virus (SIV) infection in macaques and HIV-1 infection in humans.
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Hirsch, Vanessa M., Barbara J. Campbell, Elizabeth Bailes, Robert Goeken, Charles Brown, William R. Elkins, Michael Axthelm, Michael Murphey-Corb, and Paul M. Sharp. "Characterization of a Novel Simian Immunodeficiency Virus (SIV) from L’Hoest Monkeys (Cercopithecus l’hoesti): Implications for the Origins of SIVmnd and Other Primate Lentiviruses." Journal of Virology 73, no. 2 (February 1, 1999): 1036–45. http://dx.doi.org/10.1128/jvi.73.2.1036-1045.1999.
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ABSTRACT The human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) appear to have originated by cross-species transmission of simian immunodeficiency virus (SIV) from asymptomatically infected African primates. Few of the SIVs characterized to date efficiently infect human primary lymphocytes. Interesting, two of the three identified to infect such cultures (SIVsm and SIVcpz) have appeared in human populations as genetically related HIVs. In the present study, we characterized a novel SIV isolate from an East African monkey of theCercopithecus genus, the l’hoest monkey (C. l’hoesti), which we designated SIVlhoest. This SIV isolate efficiently infected both human and macaque lymphocytes and resulted in a persistent infection of macaques, characterized by high primary virus load and a progressive decline in circulating CD4 lymphocytes, consistent with progression to AIDS. Phylogenetic analyses showed that SIVlhoest is genetically distinct from other previously characterized primate lentiviruses but clusters in the same major lineage as SIV from mandrills (SIVmnd), a West African primate species. Given the geographic distance between the ranges of l’hoest monkeys and mandrills, this may indicate that SIVmnd arose through cross-species transmission from close relatives of l’hoest monkeys that are sympatric with mandrills. These observations lend support to the hypothesis that the primate lentiviruses originated and coevolved within monkeys of the Cercopithecus genus. Regarded in this light, lentivirus infections of primates not belonging to theCercopithecus genus may have resulted from cross-species transmission in the not-too-distant past.
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de Pablo-Maiso, Lorena, Irache Echeverría, Sergio Rius-Rocabert, Lluís Luján, Dominique Garcin, Damián de Andrés, Estanislao Nistal-Villán, and Ramsés Reina. "Sendai Virus, a Strong Inducer of Anti-Lentiviral State in Ovine Cells." Vaccines 8, no. 2 (April 29, 2020): 206. http://dx.doi.org/10.3390/vaccines8020206.
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Small ruminant lentiviruses (SRLVs) are widely spread in the ovine and caprine populations, causing an incurable disease affecting animal health and production. Vaccine development is hindered owing to the high genetic heterogeneity of lentiviruses and the selection of T-cell and antibody escape mutants, requiring antigen delivery optimization. Sendai virus (SeV) is a respiratory paramyxovirus in mice that has been recognized as a potent inducer of innate immune responses in several species, including mouse and human. The aim of this study was to stimulate an innate antiviral response in ovine cells and evaluate the potential inhibitory effect upon small ruminant lentivirus (SRLV) infections. Ovine alveolar macrophages (AMs), blood-derived macrophages (BDMs), and skin fibroblasts (OSFs) were stimulated through infection with SeV encoding green fluorescent protein (GFP). SeV efficiently infected ovine cells, inducing an antiviral state in AM from SRLV naturally-infected animals, as well as in in vitro SRLV-infected BDM and OSF from non-infected animals. Supernatants from SeV-infected AM induced an antiviral state when transferred to fresh cells challenged with SRLV. Similar to SRLV, infectivity of an HIV-1-GFP lentiviral vector was also restricted in ovine cells infected with SeV. In myeloid cells, an M1-like proinflammatory polarization was observed together with an APOBEC3Z1 induction, among other lentiviral restriction factors. Our observations may boost new approximations in ameliorating the SRLV burden by stimulation of the innate immune response using SeV-based vaccine vectors.
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Sait, A., and OB Ince. "Investigation of the Epidemiology of Small Ruminant Lentivirus Infections southeast part of the Marmara region of Turkey." Journal of the Hellenic Veterinary Medical Society 73, no. 4 (January 25, 2023): 5053–60. http://dx.doi.org/10.12681/jhvms.29095.
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Small ruminant lentiviruses (SRLVs) are viral pathogens that are common in goats and sheep, affect production, and cause significant economic losses in small ruminant breeding. Caprine arthritis encephalitis virus (CAEV) and Maedi-Visna virus (MVV) are prototypes of SRLVs. Both of them affect animal health and welfare in sheep and goats and cause progressive and persistent infections in the small ruminant industry. The present study aimed to reveal the epidemiological status of lentivirus infection in the sheep region in Yalova province located in the southeast part of the Marmara region and determine the circulating genotypes by conducting the sequence analysis of the samples detected positive by a molecular method and molecular characterization of the detected field strains. To that end, 231 sheep blood samples were used between May 2016 and April 2018. Based on sampling results of the PCR test and ELISA tests, 5.62% (13/231) and 5.19% (12/231) positivity rates were found in sheep, respectively. According to the ELISA test results, a significant difference was found in terms of age groups (6 months -1 age, 1-3 age, >3 age) (χ2: 6.01; p=0.04). Furthermore, the sequence analysis of the gag gene region detected the existence of the A genotype of small ruminant lentiviruses in sheep. The data obtained from the study revealed a low seroprevalence course of SRLV infection in the study area in the absence of a systematic disease control program.
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Anis, Eman A., Madhu Dhar, Alfred M. Legendre, and Rebecca P. Wilkes. "Transduction of hematopoietic stem cells to stimulate RNA interference against feline infectious peritonitis." Journal of Feline Medicine and Surgery 19, no. 6 (June 27, 2016): 680–86. http://dx.doi.org/10.1177/1098612x16654958.
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Objectives The goals of the study were: (1) to develop and evaluate non-replicating lentivirus vectors coding for feline coronavirus (FCoV)-specific micro (mi)RNA as a potential antiviral therapy for feline infectious peritonitis (FIP); (2) to assess the feasibility of transducing hematopoietic stem cells (HSCs) with ex vivo introduction of the miRNA-expressing lentivirus vector; and (3) to assess the ability of the expressed miRNA to inhibit FCoV replication in HSCs in vitro. Methods HSCs were obtained from feline bone marrow and replicated in vitro. Three lentiviruses were constructed, each expressing a different anti-FCoV miRNA. HSCs were stably transduced with the miRNA-expressing lentivirus vector that produced the most effective viral inhibition in a feline cell line. The effectiveness of the transduction and the expression of anti-FCoV miRNA were tested by infecting the HSCs with two different strains of FCoV. The inhibition of coronavirus replication was determined by relative quantification of the inhibition of intracellular viral genomic RNA synthesis using real-time, reverse-transcription PCR. The assessment of virus replication inhibition was determined via titration of extracellular virus using the TCID50 assay. Results Inhibition of FCoV was most significant in feline cells expressing miRNA-L2 that targeted the viral leader sequence, 48 h postinfection. miRNA-L2 expression in stably transduced HSCs resulted in 90% and 92% reductions in FIPV WSU 79-1146 genomic RNA synthesis and extracellular virus production, respectively, as well as 74% and 80% reduction in FECV WSU 79-1683 genomic RNA synthesis and extracellular virus production, respectively, as compared with an infected negative control sample producing non-targeting miRNA. Conclusions and relevance These preliminary results show that genetic modification of HSCs for constitutive production of anti-coronavirus miRNA will reduce FCoV replication.
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Hötzel, Isidro. "Conservation of inner domain modules in the surface envelope glycoproteins of an ancient rabbit lentivirus and extant lentiviruses and betaretroviruses." Virology 372, no. 1 (March 2008): 201–7. http://dx.doi.org/10.1016/j.virol.2007.10.038.
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Pisoni, Giuliano, Giuseppe Bertoni, Maria Puricelli, Marina Maccalli, and Paolo Moroni. "Demonstration of Coinfection with and Recombination by Caprine Arthritis-Encephalitis Virus and Maedi-Visna Virus in Naturally Infected Goats." Journal of Virology 81, no. 10 (March 7, 2007): 4948–55. http://dx.doi.org/10.1128/jvi.00126-07.
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ABSTRACT Recombination of different strains and subtypes is a hallmark of lentivirus infections, particularly for human immunodeficiency virus, and contributes significantly to viral diversity and evolution both within individual hosts and within populations. Recombinant viruses are generated in individuals coinfected or superinfected with more than one lentiviral strain or subtype. This, however, has never been described in vivo for the prototype lentivirus maedi-visna virus of sheep and its closely related caprine counterpart, the caprine arthritis-encephalitis virus. Cross-species infections occur in animals living under natural conditions, which suggests that dual infections with small-ruminant lentiviruses (SRLVs) are possible. In this paper we describe the first documented case of coinfection and viral recombination in two naturally infected goats. DNA fragments encompassing a variable region of the envelope glycoprotein were obtained from these two animals by end-limiting dilution PCR of peripheral blood mononuclear cells or infected cocultures. Genetic analyses, including nucleotide sequencing and heteroduplex mobility assays, showed that these goats harbored two distinct populations of SRLVs. Phylogenetic analysis permitted us to assign these sequences to the maedi-visna virus group (SRLV group A) or the caprine arthritis-encephalitis virus group (SRLV group B). SimPlot analysis showed clear evidence of A/B recombination within the env gene segment of a virus detected in one of the two goats. This case provides conclusive evidence that coinfection by different strains of SRLVs of groups A and B can indeed occur and that these viruses actually recombine in vivo.
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Dooher, Julia E., and Jaisri R. Lingappa. "Conservation of a Stepwise, Energy-Sensitive Pathway Involving HP68 for Assembly of Primate Lentivirus Capsids in Cells." Journal of Virology 78, no. 4 (February 15, 2004): 1645–56. http://dx.doi.org/10.1128/jvi.78.4.1645-1656.2004.
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ABSTRACT Previously we have described a stepwise, energy-dependent pathway for human immunodeficiency virus type 1 (HIV-1) capsid assembly in a cell-free system. In this pathway, Gag polypeptides utilize the cellular factor HP68 and assemble into immature capsids by way of assembly intermediates that have defined biochemical characteristics. Here we address whether this pathway is universally conserved among primate lentiviruses and can be observed in mammalian cells. We demonstrate that HIV-2 Gag associates with human HP68 in a cell-free system and that Gag proteins of HIV-2, simian immunodeficiency virus SIVmac239, and SIVagm associate with endogenous HP68 in primate cells, as is seen for HIV-1. Analysis of primate cells expressing lentivirus Gag proteins revealed Gag-containing complexes with the same sedimentation values as seen for previously described HIV-1 assembly intermediates in the cell-free system (10S, 80-150S, and 500S). These complexes fit criteria for assembly intermediates as judged by energy sensitivity, pattern of HP68 association, and the failure of specific complexes to be formed by assembly-incompetent Gag mutants. We also demonstrate that virus-like particles released from cells do not appear to contain HP68, suggesting that HP68 is released from Gag upon completion of capsid assembly in cells, as was observed previously in the cell-free system. Together these findings support a model in which all primate lentivirus capsids assemble by a conserved pathway of HP68-containing, energy-dependent assembly intermediates that have specific biochemical features.
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Larrea, Esther, Celia Fernández-Rubio, José Peña-Guerrero, Elizabeth Guruceaga, and Paul A. Nguewa. "The BRCT Domain from the Homologue of the Oncogene PES1 in Leishmania major (LmjPES) Promotes Malignancy and Drug Resistance in Mammalian Cells." International Journal of Molecular Sciences 23, no. 21 (October 30, 2022): 13203. http://dx.doi.org/10.3390/ijms232113203.
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Around 15% of cancer cases are attributable to infectious agents. Epidemiological studies suggest that an association between leishmaniasis and cancer does exist. Recently, the homologue of PES1 in Leishmania major (LmjPES) was described to be involved in parasite infectivity. Mammalian PES1 protein has been implicated in cellular processes like cell cycle regulation. Its BRCT domain has been identified as a key factor in DNA damage-responsive checkpoints. This work aimed to elucidate the hypothetical oncogenic implication of BRCT domain from LmjPES in host cells. We generated a lentivirus carrying this BRCT domain sequence (lentiBRCT) and a lentivirus expressing the luciferase protein (lentiLuc), as control. Then, HEK293T and NIH/3T3 mammalian cells were infected with these lentiviruses. We observed that the expression of BRCT domain from LmjPES conferred to mammal cells in vitro a greater replication rate and higher survival. In in vivo experiments, we observed faster tumor growth in mice inoculated with lentiBRCT respect to lentiLuc HEK293T infected cells. Moreover, the lentiBRCT infected cells were less sensitive to the genotoxic drugs. Accordingly, gene expression profiling analysis revealed that BRCT domain from LmjPES protein altered the expression of proliferation- (DTX3L, CPA4, BHLHE41, BMP2, DHRS2, S100A1 and PARP9), survival- (BMP2 and CARD9) and chemoresistance-related genes (DPYD, Dok3, DTX3L, PARP9 and DHRS2). Altogether, our results reinforced the idea that in eukaryotes, horizontal gene transfer might be also achieved by parasitism like Leishmania infection driving therefore to some crucial biological changes such as proliferation and drug resistance.
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McIntosh, E. M., and R. H. Haynes. "HIV and human endogenous retroviruses: an hypothesis with therapeutic implications." Acta Biochimica Polonica 43, no. 4 (December 31, 1996): 583–92. http://dx.doi.org/10.18388/abp.1996_4454.
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The enzyme dUTP pyrophosphatase (dUTPase, EC 3.6.1.23) is essential for cellular DNA replication and cell viability by virtue of its role in reducing the availability of dUTP as a substrate for DNA polymerases. Several members of the onco- and lentivirus families of retroviruses encode dUTPases and mutant strains of these viruses defective in this enzyme exhibit suboptimal replication kinetics. Among the lentiviruses there exists a surprising phylogenetic discontinuity in the distribution of dUTPase genes: non-primate viruses (EIAV, CAEV, FIV, visna) contain such genes whereas the primate viruses (HIVs, SIVs) do not. The reason for this difference is unknown. We suggest the following explanation: (1) the nuclear and mitochondrial compartmentalization of the mammalian dUTPase, combined with the cytoplasmic location of ribonucleotide reductase, leads to the net synthesis of dUTP, together with dCTP, dGTP and dATP in the cytoplasm; (2) this combination of dNTPs serves as a "toxic cocktail" for viral replication by virtue of its ability to promote the synthesis of uracil-substituted DNA; (3) many viruses have adapted to this challenge by encoding dUTPases that are free of normal cellular regulatory constraints; and (4) the fortuitous expression of a dUTPase encoded by one or more human endogenous retroviruses (HERVs) has led to the evolutionary loss of the putative ancestral dUTPase gene of primate lentiviruses. Thus, we propose that efficient replication of HIV in humans depends upon expression of a dUTPase encoded by an endogenous retrovirus. If this proposal is correct, then the entry of HIV into target cells is necessary, but not sufficient, for replication of the virus in humans.