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Joris Paris, Joëlle Tobaly-Tapiero, Marie-Lou Giron, Julien Burlaud-Gaillard, Florence Buseyne, Philippe Roingeard, Pascale Lesage, Alessia Zamborlini, Ali Saïb
BACKGROUND: Nuclear localization of Gag is a property shared by many retroviruses and retrotransposons. The importance of this stage for retroviral replication is still unknown, but studies on the Rous Sarcoma virus indicate that Gag might select the viral RNA genome for packaging in the nucleus. In the case of Foamy viruses, genome encapsidation is mediated by Gag C-terminal domain (CTD), which harbors three clusters of glycine and arginine residues named GR boxes (GRI-III). In this study we investigated how PFV Gag subnuclear distribution might be regulated...
July 11, 2018: Retrovirology
Art F Y Poon, Jessica L Prodger, Briana A Lynch, Jun Lai, Steven J Reynolds, Jingo Kasule, Adam A Capoferri, Susanna L Lamers, Christopher W Rodriguez, Daniel Bruno, Stephen F Porcella, Craig Martens, Thomas C Quinn, Andrew D Redd
BACKGROUND: The ability of HIV-1 to integrate into the genomes of quiescent host immune cells, establishing a long-lived latent viral reservoir (LVR), is the primary obstacle to curing these infections. Quantitative viral outgrowth assays (QVOAs) are the gold standard for estimating the size of the replication-competent HIV-1 LVR, measured by the number of infectious units per million (IUPM) cells. QVOAs are time-consuming because they rely on culturing replicate wells to amplify the production of virus antigen or nucleic acid to reproducibly detectable levels...
July 5, 2018: Retrovirology
Danica D Wiredja, Caroline O Tabler, Daniela M Schlatzer, Ming Li, Mark R Chance, John C Tilton
BACKGROUND: Viral reprogramming of host cells enhances replication and is initiated by viral interaction with the cell surface. Upon human immunodeficiency virus (HIV) binding to CD4+ T cells, a signal transduction cascade is initiated that reorganizes the actin cytoskeleton, activates transcription factors, and alters mRNA splicing pathways. METHODS: We used a quantitative mass spectrometry-based phosphoproteomic approach to investigate signal transduction cascades initiated by CCR5-tropic HIV, which accounts for virtually all transmitted viruses and the vast majority of viruses worldwide...
July 3, 2018: Retrovirology
Hayato Murakoshi, Chengcheng Zou, Nozomi Kuse, Tomohiro Akahoshi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka, Tomáš Hanke, Masafumi Takiguchi
BACKGROUND: Development of AIDS vaccines for effective prevention of circulating HIV-1 is required, but no trial has demonstrated definitive effects on the prevention. Several recent T-cell vaccine trials showed no protection against HIV-1 acquisition although the vaccines induced HIV-1-specific T-cell responses, suggesting that the vaccine-induced T cells have insufficient capacities to suppress HIV-1 replication and/or cross-recognize circulating HIV-1. Therefore, it is necessary to develop T-cell vaccines that elicit T cells recognizing shared protective epitopes with strong ability to suppress HIV-1...
July 3, 2018: Retrovirology
Defang Zhou, Jingwen Xue, Shuhai He, Xusheng Du, Jing Zhou, Chengui Li, Libo Huang, Venugopal Nair, Yongxiu Yao, Ziqiang Cheng
BACKGROUND: Co-infection with avian leukosis virus subgroup J and reticuloendotheliosis virus induces synergistic pathogenic effects and increases mortality. However, the role of exosomal miRNAs in the molecular mechanism of the synergistic infection of the two viruses remains unknown. RESULTS: In this study, exosomal RNAs from CEF cells infected with ALV-J, REV or both at the optimal synergistic infection time were analysed by Illumina RNA deep sequencing. A total of 54 (23 upregulated and 31 downregulated) and 16 (7 upregulated and 9 downregulated) miRNAs were identified by comparing co-infection with two viruses, single-infected ALV-J and REV, respectively...
July 3, 2018: Retrovirology
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No abstract text is available yet for this article.
July 2, 2018: Retrovirology
Shringar Rao, Raquel Amorim, Meijuan Niu, Abdelkrim Temzi, Andrew J Mouland
BACKGROUND: The ability of human immunodeficiency virus type 1 (HIV-1) to form a stable viral reservoir is the major obstacle to an HIV-1 cure and post-transcriptional events contribute to the maintenance of viral latency. RNA surveillance proteins such as UPF1, UPF2 and SMG6 affect RNA stability and metabolism. In our previous work, we demonstrated that UPF1 stabilises HIV-1 genomic RNA (vRNA) and enhances its translatability in the cytoplasm. Thus, in this work we evaluated the influence of RNA surveillance proteins on vRNA expression and, as a consequence, viral reactivation in cells of the lymphoid lineage...
June 28, 2018: Retrovirology
Jakub Chojnacki, Christian Eggeling
Super-resolution fluorescence microscopy combines the ability to observe biological processes beyond the diffraction limit of conventional light microscopy with all advantages of the fluorescence readout such as labelling specificity and non-invasive live-cell imaging. Due to their subdiffraction size (< 200 nm) viruses are ideal candidates for super-resolution microscopy studies, and Human Immunodeficiency Virus type 1 (HIV-1) is to date the most studied virus by this technique. This review outlines principles of different super-resolution techniques as well as their advantages and disadvantages for virological studies, especially in the context of live-cell imaging applications...
June 8, 2018: Retrovirology
Stuart Turville, Anthony Kelleher
No abstract text is available yet for this article.
May 24, 2018: Retrovirology
Andrey Ivanov, Xionghao Lin, Tatiana Ammosova, Andrey V Ilatovskiy, Namita Kumari, Hatajai Lassiter, Nowah Afangbedji, Xiaomei Niu, Michael G Petukhov, Sergei Nekhai
BACKGROUND: HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue and by PKR on Tat Ser-46 residue. Here we analyzed Tat phosphorylation in cultured cells and its functionality. RESULTS: Mass spectrometry analysis showed primarily Tat Ser-16 phosphorylation in cultured cells. In vitro, CDK2/cyclin E predominantly phosphorylated Tat Ser-16 and PKR-Tat Ser-46. Alanine mutations of either Ser-16 or Ser-46 decreased overall Tat phosphorylation...
May 23, 2018: Retrovirology
Steven J Smith, Xue Zhi Zhao, Terrence R Burke, Stephen H Hughes
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are the class of antiretroviral (ARV) drugs most recently approved by the FDA for the treatment of HIV-1 infections. INSTIs block the strand transfer reaction catalyzed by HIV-1 integrase (IN) and have been shown to potently inhibit infection by wild-type HIV-1. Of the three current FDA-approved INSTIs, Dolutegravir (DTG), has been the most effective, in part because treatment does not readily select for resistant mutants. However, recent studies showed that when INSTI-experienced patients are put on a DTG-salvage therapy, they have reduced response rates...
May 16, 2018: Retrovirology
Carmen Ledesma-Feliciano, Sarah Hagen, Ryan Troyer, Xin Zheng, Esther Musselman, Dragana Slavkovic Lukic, Ann-Mareen Franke, Daniel Maeda, Jörg Zielonka, Carsten Münk, Guochao Wei, Sue VandeWoude, Martin Löchelt
BACKGROUND: Hosts are able to restrict viral replication to contain virus spread before adaptive immunity is fully initiated. Many viruses have acquired genes directly counteracting intrinsic restriction mechanisms. This phenomenon has led to a co-evolutionary signature for both the virus and host which often provides a barrier against interspecies transmission events. Through different mechanisms of action, but with similar consequences, spumaviral feline foamy virus (FFV) Bet and lentiviral feline immunodeficiency virus (FIV) Vif counteract feline APOBEC3 (feA3) restriction factors that lead to hypermutation and degradation of retroviral DNA genomes...
May 16, 2018: Retrovirology
Georges Khoury, Talia M Mota, Shuang Li, Carolin Tumpach, Michelle Y Lee, Jonathan Jacobson, Leigh Harty, Jenny L Anderson, Sharon R Lewin, Damian F J Purcell
BACKGROUND: Different classes of latency reversing agents (LRAs) are being evaluated to measure their effects in reactivating HIV replication from latently infected cells. A limited number of studies have demonstrated additive effects of LRAs with the viral protein Tat in initiating transcription, but less is known about how LRAs interact with Tat, particularly through basic residues that may be post-translationally modified to alter the behaviour of Tat for processive transcription and co-transcriptional RNA processing...
May 11, 2018: Retrovirology
Paul D Bieniasz, Sebla B Kutluay
Virtually every step of HIV-1 replication and numerous cellular antiviral defense mechanisms are regulated by the binding of a viral or cellular RNA-binding protein (RBP) to distinct sequence or structural elements on HIV-1 RNAs. Until recently, these protein-RNA interactions were studied largely by in vitro binding assays complemented with genetics approaches. However, these methods are highly limited in the identification of the relevant targets of RBPs in physiologically relevant settings. Development of crosslinking-immunoprecipitation sequencing (CLIP) methodology has revolutionized the analysis of protein-nucleic acid complexes...
May 2, 2018: Retrovirology
Daniel Blanco-Melo, Robert J Gifford, Paul D Bieniasz
BACKGROUND: About 10% of the mouse genome is composed of endogenous retroviruses (ERVs) that represent a molecular fossil record of past retroviral infections. One such retrovirus, murine ERV-L (MuERV-L) is an env-deficient ERV that has undergone episodic proliferation, with the most recent amplification occurring ~ 2 million years ago. MuERV-L related sequences have been co-opted by mice for antiretroviral defense, and possibly as promoters for some genes that regulate totipotency in early mouse embryos...
May 2, 2018: Retrovirology
Rita Hleihel, Behzad Khoshnood, Ingrid Dacklin, Hayssam Omran, Carine Mouawad, Zeina Dassouki, Marwan El-Sabban, Margret Shirinian, Caroline Grabbe, Ali Bazarbachi
BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy secondary to chronic human T-cell lymphotropic virus 1 infection, triggered by the virally encoded oncoprotein Tax. The transforming activity and subcellular localization of Tax is strongly influenced by posttranslational modifications, among which ubiquitylation and SUMOylation have been identified as key regulators of the nuclear/cytoplasmic shuttling of Tax, as well as its ability to activate NF-κB signaling...
April 17, 2018: Retrovirology
Fu-Hsien Yu, Chin-Tien Wang
BACKGROUND: HIV-1 protease (PR) activation is triggered by Gag-Pol dimerization. Premature PR activation results in reduced virion yields due to enhanced Gag cleavage. A p6* transframe peptide located directly upstream of protease is believed to play a modulating role in PR activation. Previous reports indicate that the C-terminal p6* tetra-peptide prevents premature PR activation triggered by a leucine zipper (LZ) dimerization motif inserted in the deleted p6* region. To clarify the involvement of C-terminal p6* residues in mitigating enhanced LZ-incurred Gag processing, we engineered constructs containing C-terminal p6* residue substitutions with and without a mutation blocking the p6*/PR cleavage site, and created other Gag or p6* domain-removing constructs...
April 14, 2018: Retrovirology
Yoriyuki Konno, Shumpei Nagaoka, Izumi Kimura, Keisuke Yamamoto, Yumiko Kagawa, Ryuichi Kumata, Hirofumi Aso, Mahoko Takahashi Ueda, So Nakagawa, Tomoko Kobayashi, Yoshio Koyanagi, Kei Sato
BACKGROUND: The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) gene family appears only in mammalian genomes. Some A3 proteins can be incorporated into progeny virions and inhibit lentiviral replication. In turn, the lentiviral viral infectivity factor (Vif) counteracts the A3-mediated antiviral effect by degrading A3 proteins. Recent investigations have suggested that lentiviral vif genes evolved to combat mammalian APOBEC3 proteins, and have further proposed that the Vif-A3 interaction may help determine the co-evolutionary history of cross-species lentiviral transmission in mammals...
April 10, 2018: Retrovirology
Christine Rouzioux, Véronique Avettand-Fenoël
Among the different markers of HIV persistence in infected cells, total HIV DNA is to date the most widely used. It allows an overall quantification of all viral forms of HIV DNA in infected cells, each playing a different role in HIV replication and pathophysiology. The real-time PCR technology is to date, a precise, sensitive and reproducible technology that allows the description of the distribution of HIV infected cells in blood and tissues. The objective of this review is to present some examples which show the interest to quantify total HIV DNA levels...
April 3, 2018: Retrovirology
Dehua Liu, Hongyun Wang, Mizuki Yamamoto, Jiping Song, Rui Zhang, Qingling Du, Yasushi Kawaguchi, Jun-Ichiro Inoue, Zene Matsuda
BACKGROUND: The native pre-fusion structure of gp120/gp41 complex of human immunodeficiency virus type 1 was recently revealed. In the model, the helices of gp41 (α6, α7, α8, and α9) form a four-helix collar underneath trimeric gp120. Gp41 is a class I fusion protein and mediates membrane fusion by forming a post-fusion structure called the six-helix bundle (6HB). The comparison of the pre- and post-fusion structures revealed the large conformational changes in gp41 during the antiparallel packing of the N- and C-terminal heptad repeats (NHRs and CHRs) in membrane fusion...
April 2, 2018: Retrovirology
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