Littérature scientifique sur le sujet « HAdV5 E1A »
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Articles de revues sur le sujet "HAdV5 E1A"
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Singh, Gurdeep, Ashrafali M. Ismail, Jeong Yoon Lee, Mirja Ramke, Ji Sun Lee, David W. Dyer, Donald Seto, Jaya Rajaiya et and James Chodosh. « Divergent Evolution of E1A CR3 in Human Adenovirus Species D ». Viruses 11, no 2 (8 février 2019) : 143. http://dx.doi.org/10.3390/v11020143.
Texte intégralRésumé :
Adenovirus E1A is the first viral protein expressed during infection. E1A controls critical aspects of downstream viral gene expression and cell cycle deregulation, and its function is thought to be highly conserved among adenoviruses. Various bioinformatics analyses of E1A from 38 human adenoviruses of species D (HAdV-D), including likelihood clade model partitioning, provided highly significant evidence of divergence of HAdV-Ds into two distinct groups for the conserved region 3 (CR3), present only in the E1A 13S isoform. This variance within E1A 13S of HAdV-Ds was not found in any other human adenovirus (HAdV) species. By protein sequence and structural analysis, the zinc finger motif of E1A CR3, previously shown as critical for transcriptional activation, showed the greatest differences. Subsequent codon usage bias analysis revealed substantial divergence in E1A 13S between the two groups of HAdV-Ds, suggesting that these two sub-groups of HAdV-D evolved under different cellular conditions. Hence, HAdV-D E1A embodies a previously unappreciated evolutionary divergence among HAdVs.
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Kim, Misoon, Mi Young Lim et GwangPyo Ko. « Enhancement of Enteric Adenovirus Cultivation by Viral Transactivator Proteins ». Applied and Environmental Microbiology 76, no 8 (5 février 2010) : 2509–16. http://dx.doi.org/10.1128/aem.02224-09.
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ABSTRACT Human enteric adenoviruses (HAdVs; serotypes 40 and 41) are important waterborne and food-borne pathogens. However, HAdVs are fastidious, are difficult to cultivate, and do not produce a clear cytopathic effect during cell culture within a reasonable time. Thus, we examined whether the viral transactivator proteins cytomegalovirus (CMV) IE1 and hepatitis B virus (HBV) X promoted the multiplication of HAdVs. Additionally, we constructed a new 293 cell line expressing CMV IE1 protein for cultivation assays. We analyzed the nucleic acid sequences of the promoter regions of both E1A and hexon genes, which are considered to be the most important regions for HAdV replication. Expression of either HBV X or CMV IE1 protein significantly increased the promoter activities of E1A and hexon genes of HAdVs by as much as 14-fold during cell cultivation. The promotion of HAdV expression was confirmed by increased levels of both adenoviral DNA and mRNA expression. Finally, the newly developed 293 cell line expressing CMV IE1 protein showed an increase in viral DNA ranging from 574% to 619% compared with the conventional 293 cell line. These results suggest that the newly constructed cell line could be useful for efficient cultivation and research of fastidious HAdVs.
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Ip, Wing-Hang, Britta Wilkens, Anastasia Solomatina, Judith Martin, Michael Melling, Paloma Hidalgo, Luca D. Bertzbach, Thomas Speiseder et Thomas Dobner. « Differential Regulation of Cellular FAM111B by Human Adenovirus C Type 5 E1 Oncogenes ». Viruses 13, no 6 (28 mai 2021) : 1015. http://dx.doi.org/10.3390/v13061015.
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The adenovirus type 5 (HAdV-C5) E1 transcription unit encodes regulatory proteins that are essential for viral replication and transformation. Among these, E1A and E1B-55K act as key multifunctional HAdV-C5 proteins involved in various steps of the viral replication cycle and in virus-induced cell transformation. In this context, HAdV-C5-mediated dysregulations of cellular factors such as the tumor suppressors p53 and pRB have been intensively investigated. However, cellular components of downstream events that could affect infection and viral transformation are widely unknown. We recently observed that cellular FAM111B is highly regulated in an E1A-dependent fashion. Intriguingly, previous reports suggest that FAM111B might play roles in tumorigenesis, but its exact functions are not known to date. Here, we set out to investigate the role of FAM111B in HAdV-C5 infections. We found that (i) FAM111B levels are upregulated early and downregulated late during infection, that (ii) FAM111B expression is differentially regulated, that (iii) FAM111B expression levels depend on the presence of E1B-55K and E4orf6 and that (iv) a FAM111B knockdown increases HAdV-C5 replication. Our data indicate that FAM111B acts as an anti-adenoviral host factor that is involved in host cell defense mechanisms in productive HAdV-C5 infection. Moreover, these findings suggest that FAM111B might play an important role in the host antiviral immune response that is counteracted by HAdV-C5 E1B-55K and E4orf6 oncoproteins.
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Zhang, Ali, Tanner Tessier, Kristianne Galpin, Cason King, Steven Gameiro, Wyatt Anderson, Ahmed Yousef, Wen Qin, Shawn Li et Joe Mymryk. « The Transcriptional Repressor BS69 is a Conserved Target of the E1A Proteins from Several Human Adenovirus Species ». Viruses 10, no 12 (22 novembre 2018) : 662. http://dx.doi.org/10.3390/v10120662.
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Early region 1A (E1A) is the first viral protein produced upon human adenovirus (HAdV) infection. This multifunctional protein transcriptionally activates other HAdV early genes and reprograms gene expression in host cells to support productive infection. E1A functions by interacting with key cellular regulatory proteins through short linear motifs (SLiMs). In this study, the molecular determinants of interaction between E1A and BS69, a cellular repressor that negatively regulates E1A transactivation, were systematically defined by mutagenesis experiments. We found that a minimal sequence comprised of MPNLVPEV, which contains a conserved PXLXP motif and spans residues 112–119 in HAdV-C5 E1A, was necessary and sufficient in binding to the myeloid, Nervy, and DEAF-1 (MYND) domain of BS69. Our study also identified residues P113 and L115 as critical for this interaction. Furthermore, the HAdV-C5 and -A12 E1A proteins from species C and A bound BS69, but those of HAdV-B3, -E4, -D9, -F40, and -G52 from species B, E, D, F, and G, respectively, did not. In addition, BS69 functioned as a repressor of E1A-mediated transactivation, but only for HAdV-C5 and HAdV-A12 E1A. Thus, the PXLXP motif present in a subset of HAdV E1A proteins confers interaction with BS69, which serves as a negative regulator of E1A mediated transcriptional activation.
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Roy, Soumitra, David S. Clawson, Virginie S. Adam, Angelica Medina et James M. Wilson. « Construction of gene transfer vectors based on simian adenovirus 7 ». Journal of General Virology 92, no 8 (1 août 2011) : 1749–53. http://dx.doi.org/10.1099/vir.0.032300-0.
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The complete nucleotide sequence of an isolate of simian adenovirus 7 (SAdV-7) was determined. The genome organization of this isolate was found to be similar to that of other primate adenoviruses with two principal notable points: severe truncation of the E1A and E1B 19K proteins and an E3 region encoding only the 12.5K homologue. The viral gene products of SAdV-7 are most closely related to simian adenovirus 1 (SAdV-1), and like SAdV-1, are related to the human adenovirus species HAdV-F, such as the enteric adenoviruses HAdV-40 and HAdV-41 and the recently defined HAdV-G (HAdV-52). Two kinds of gene transfer vectors were made: a replication-competent SAdV-7-based vector with no genomic deletion, and a standard replication-incompetent vector deleted for E1. Importantly, the E1-deleted vector could be propagated to high titre by trans-complementation in human HEK 293 cells.
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Prusinkiewicz, Martin A., Jessie Tu, Mackenzie J. Dodge, Katelyn M. MacNeil, Sandi Radko-Juettner, Gregory J. Fonseca, Peter Pelka et Joe S. Mymryk. « Differential Effects of Human Adenovirus E1A Protein Isoforms on Aerobic Glycolysis in A549 Human Lung Epithelial Cells ». Viruses 12, no 6 (3 juin 2020) : 610. http://dx.doi.org/10.3390/v12060610.
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Viruses alter a multitude of host-cell processes to create a more optimal environment for viral replication. This includes altering metabolism to provide adequate substrates and energy required for replication. Typically, viral infections induce a metabolic phenotype resembling the Warburg effect, with an upregulation of glycolysis and a concurrent decrease in cellular respiration. Human adenovirus (HAdV) has been observed to induce the Warburg effect, which can be partially attributed to the adenovirus protein early region 4, open reading frame 1 (E4orf1). E4orf1 regulates a multitude of host-cell processes to benefit viral replication and can influence cellular metabolism through the transcription factor avian myelocytomatosis viral oncogene homolog (MYC). However, E4orf1 does not explain the full extent of Warburg-like HAdV metabolic reprogramming, especially the accompanying decrease in cellular respiration. The HAdV protein early region 1A (E1A) also modulates the function of the infected cell to promote viral replication. E1A can interact with a wide variety of host-cell proteins, some of which have been shown to interact with metabolic enzymes independently of an interaction with E1A. To determine if the HAdV E1A proteins are responsible for reprogramming cell metabolism, we measured the extracellular acidification rate and oxygen consumption rate of A549 human lung epithelial cells with constitutive endogenous expression of either of the two major E1A isoforms. This was followed by the characterization of transcript levels for genes involved in glycolysis and cellular respiration, and related metabolic pathways. Cells expressing the 13S encoded E1A isoform had drastically increased baseline glycolysis and lower maximal cellular respiration than cells expressing the 12S encoded E1A isoform. Cells expressing the 13S encoded E1A isoform exhibited upregulated expression of glycolysis genes and downregulated expression of cellular respiration genes. However, tricarboxylic acid cycle genes were upregulated, resembling anaplerotic metabolism employed by certain cancers. Upregulation of glycolysis and tricarboxylic acid cycle genes was also apparent in IMR-90 human primary lung fibroblast cells infected with a HAdV-5 mutant virus that expressed the 13S, but not the 12S encoded E1A isoform. In conclusion, it appears that the two major isoforms of E1A differentially influence cellular glycolysis and oxidative phosphorylation and this is at least partially due to the altered regulation of mRNA expression for the genes in these pathways.
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Bürck, Carolin, Andreas Mund, Julia Berscheminski, Lisa Kieweg, Sarah Müncheberg, Thomas Dobner et Sabrina Schreiner. « KAP1 Is a Host Restriction Factor That Promotes Human Adenovirus E1B-55K SUMO Modification ». Journal of Virology 90, no 2 (4 novembre 2015) : 930–46. http://dx.doi.org/10.1128/jvi.01836-15.
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ABSTRACTOnce transported to the replication sites, human adenoviruses (HAdVs) need to ensure decondensation and transcriptional activation of their viral genomes to synthesize viral proteins and initiate steps to reprogram the host cell for viral replication. These early stages during adenoviral infection are poorly characterized but represent a decisive moment in the establishment of a productive infection. Here, we identify a novel host viral restriction factor, KAP1. This heterochromatin-associated transcription factor regulates the dynamic organization of the host chromatin structure via its ability to influence epigenetic marks and chromatin compaction. In response to DNA damage, KAP1 is phosphorylated and functionally inactive, resulting in chromatin relaxation. We discovered that KAP1 posttranslational modification is dramatically altered during HAdV infection to limit the antiviral capacity of this host restriction factor, which represents an essential step required for efficient viral replication. Conversely, we also observed during infection an HAdV-mediated decrease of KAP1 SUMO moieties, known to promote chromatin decondensation events. Based on our findings, we provide evidence that HAdV induces KAP1 deSUMOylation to minimize epigenetic gene silencing and to promote SUMO modification of E1B-55K by a so far unknown mechanism.IMPORTANCEHere we describe a novel cellular restriction factor for human adenovirus (HAdV) that sheds light on very early modulation processes in viral infection. We reported that chromatin formation and cellular SWI/SNF chromatin remodeling play key roles in HAdV transcriptional regulation. We observed that the cellular chromatin-associated factor and epigenetic reader SPOC1 represses HAdV infection and gene expression. Here, we illustrate the role of the SPOC1-interacting factor KAP1 during productive HAdV growth. KAP1 binds to the viral E1B-55K protein, promoting its SUMO modification, therefore illustrating a crucial step for efficient viral replication. Simultaneously, KAP1 posttranslational modification is dramatically altered during infection. We observed an HAdV-mediated decrease in KAP1 SUMOylation, known to promote chromatin decondensation events. These findings indicate that HAdV induces the loss of KAP1 SUMOylation to minimize epigenetic gene silencing and to promote the SUMO modification of E1B-55K by a so far unknown mechanism.
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Avvakumov, Nikita, Russ Wheeler, Jean Claude D'Halluin et Joe S. Mymryk. « Comparative Sequence Analysis of the Largest E1A Proteins of Human and Simian Adenoviruses ». Journal of Virology 76, no 16 (15 août 2002) : 7968–75. http://dx.doi.org/10.1128/jvi.76.16.7968-7975.2002.
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ABSTRACT The early region 1A (E1A) gene is the first gene expressed after infection with adenovirus and has been most extensively characterized in human adenovirus type 5 (hAd5). The E1A proteins interact with numerous cellular regulatory proteins, influencing a variety of transcriptional and cell cycle events. For this reason, these multifunctional proteins have been useful as tools for dissecting pathways regulating cell growth and gene expression. Despite the large number of studies using hAd5 E1A, relatively little is known about the function of the E1A proteins of other adenoviruses. In 1985, a comparison of E1A sequences from three human and one simian adenovirus identified three regions with higher overall levels of sequence conservation designated conserved regions (CR) 1, 2, and 3. As expected, these regions are critical for a variety of E1A functions. Since that time, the sequences of several other human and simian adenovirus E1A proteins have been determined. Using these, and two additional sequences that we determined, we report here a detailed comparison of the sequences of 15 E1A proteins representing each of the six hAd subgroups and several simian adenoviruses. These analyses refine the positioning of CR1, 2, and 3; define a fourth CR located near the carboxyl terminus of E1A; and suggest several new functions for E1A.
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Dalidowska, Iga, Olga Gazi, Dorota Sulejczak, Maciej Przybylski et Pawel Bieganowski. « Heat Shock Protein 90 Chaperones E1A Early Protein of Adenovirus 5 and Is Essential for Replication of the Virus ». International Journal of Molecular Sciences 22, no 4 (18 février 2021) : 2020. http://dx.doi.org/10.3390/ijms22042020.
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Adenovirus infections tend to be mild, but they may pose a serious threat for young and immunocompromised individuals. The treatment is complicated because there are no approved safe and specific drugs for adenovirus infections. Here, we present evidence that 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG), an inhibitor of Hsp90 chaperone, decreases the rate of human adenovirus 5 (HAdV-5) replication in cell cultures by 95%. 17-AAG inhibited the transcription of early and late genes of HAdV-5, replication of viral DNA, and expression of viral proteins. 6 h after infection, Hsp90 inhibition results in a 6.3-fold reduction of the newly synthesized E1A protein level without a decrease in the E1A mRNA level. However, the Hsp90 inhibition does not increase the decay rate of the E1A protein that was constitutively expressed in the cell before exposure to the inhibitor. The co-immunoprecipitation proved that E1A protein interacted with Hsp90. Altogether, the presented results show, for the first time. that Hsp90 chaperones newly synthesized, but not mature, E1A protein. Because E1A serves as a transcriptional co-activator of adenovirus early genes, the anti-adenoviral activity of the Hsp90 inhibitor might be explained by the decreased E1A level.
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van Olphen, Alberto L., et Suresh K. Mittal. « Development and Characterization of Bovine × Human Hybrid Cell Lines That Efficiently Support the Replication of both Wild-Type Bovine and Human Adenoviruses and Those with E1 Deleted ». Journal of Virology 76, no 12 (15 juin 2002) : 5882–92. http://dx.doi.org/10.1128/jvi.76.12.5882-5892.2002.
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ABSTRACT The 293 cell line that was generated by transforming human embryonic kidney cells with human adenovirus type 5 (HAV5) early region 1 (E1) sequences is an excellent host for generating and growing HAV5 recombinants with E1 deleted, but it does not support the replication of bovine adenovirus type 3 (BAV3). Madin-Darby bovine kidney (MDBK), an established bovine cell line, is an excellent host for growing and plaquing BAV3. For the purpose of combining the unique characteristics of these two cell lines (293 and MDBK), we generated a number of bovine × human hybrid (BHH) cell lines. Comparison of three BHH hybrid clones—BHH3, BHH8, and BHH2C—with 293-Puro (puromycin-resistant 293 cells) and MDBK-Neo (G418-resistant MDBK cells) cell lines for total cellular DNA content, species-specific surface markers, isoenzyme analysis, and karyotyping indicate that they are hybrid in nature. BHH clones constitutively expressed the E1 proteins (E1A, E1B-21kDa, and E1B-55kDa) of HAV5 and efficiently supported the replication of both wild-type and replication-incompetent bovine or human adenoviruses. Transient gene expression experiments with a plasmid encoding the bacterial β-galactosidase gene demonstrated that BHH cell hybrids seem to have better transfection efficiencies than either of the parental cell lines. These cell lines will be useful for isolating and growing replication-competent human or bovine adenovirus recombinants with E1 deleted and for the study of cellular or viral factors important for viral replication. The development of somatic cell hybrids appears to be a simple way of combining some of the desirable characteristics present separately in two parental cell lines.
Thèses sur le sujet "HAdV5 E1A"
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Fiedler, Marie [Verfasser]. « Characterization of HAdV-C5 E4orf6 as a negative regulator of E1B-55K SUMOylation / Marie Fiedler ». Hamburg : Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky, 2020. http://d-nb.info/1227582358/34.
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DE, OLIVEIRA LOPES CALCADA EDUARDO PAULO. « Intrinsically disordered proteins - from sample preparation to molecular basis of function ». Doctoral thesis, 2014. http://hdl.handle.net/2158/836300.
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Olanubi, Oladunni. « Exploitation of human RuvBL1 by HAdV E1A to inhibit interferon response for efficient viral growth ». 2017. http://hdl.handle.net/1993/31993.
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E1A of human adenovirus is the first gene product expressed during viral infection and serves as a preliminary step for efficient viral replication. Other early gene products include early proteins designated as E2, E3, and E4 are also made, which together with E1A prepare the infected cell for replication of the viral genome. Various studies have elucidated that E1A functions largely as a transcriptional regulator and can interact with a host of cellular modulators to enhance replication of the virus. RuvBL1, a chromatin remodeling protein involved in a host of cellular functions such as transcriptional regulation and host cell immune response has been shown to bind to E1A. My results identify RuvBL1 as an E1A binding protein and show that E1A is a direct binding partner of RuvBL1. I demonstrate that RuvBL1 plays a role in the growth of adenovirus, as knockdown of RuvBL1 negatively affects the growth of the virus and reveals that RuvBL1 functions as a viral growth enhancer. Finally, I identify a possible role of E1A’s inhibition of interferon response in a RuvBL1 dependent manner.February 2017
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OLIVEIRA, NOGUEIRA MARCELA CRISTINA. « Characterization of heterogeneous viral proteins by NMR methods : Human Adenovirus E1A and Human papillomavirus E7 proteins ». Doctoral thesis, 2016. http://hdl.handle.net/2158/1074811.
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HPV-16 E7 and HAdV-E1A proteins have been studied for years and despite documented attempts the characterization of these proteins either through NMR or X-ray crystallography failed due to their heterogeneous structural and dynamic properties.
Thanks to the recently developed NMR approach to characterize highly heterogeneous proteins, in combination with clever sample preparation strategies, it was possible to complete the high resolution characterization through NMR of both, HPV16-E7 as well as HAdV-E1A. The information obtained, can now be used by the scientific community to answer the many open questions on the molecular determinants of the function of these two distinct proteins that are able to hijack cell regulation by a closely related mechanism. Indeed, the example of the high resolution study of one of the key post-translational modifications linked to the oncogenic process reported here just represents the first example of many studies that now can be performed taking advantage of the available NMR chemical shift assignment. This information can in turn be used to design innovative drugs that target, instead of well-structured proteins, these two IDPs.