Retrovirology最新文献

{"title":"The HIV-1 gag p6: a promising target for therapeutic intervention.","authors":"Xiaowei Chen, Xiao Wang","doi":"10.1186/s12977-024-00633-2","DOIUrl":"10.1186/s12977-024-00633-2","url":null,"abstract":"<p><p>The p6 domain of the Gag precursors (Gag p6) in human immunodeficiency virus type 1 (HIV-1) plays multifunctional roles in the viral life cycle. It utilizes the endosomal sorting complex required for transport (ESCRT) system to facilitate viral budding and release from the plasma membrane through the interactions with the ESCRT-I component tumor susceptibility gene 101 (TSG101) and with the ALG-2 interacting protein X (ALIX). Moreover, Gag p6 contributes to viral replication by a range of posttranslational modifications such as SUMOylation, ubiquitination and phosphorylation. Additionally, Gag p6 also mediates the incorporation of the accessory protein Vpr into virions, thereby promoting Vpr-induced viral replication. However, less attention is focused on Gag p6 as therapeutic intervention. This review focuses on the structures and diverse functions of Gag p6 in viral replication, host cells, and pathogenesis. Additionally, several challenges were also discussed in studying the structure of Gag p6 and its interactions with partners. Consequently, it concludes that the Gag p6 represents an attractive target for the development of antiretroviral drugs, and efforts to develop p6-targeted antiretrovirals are expected to undergo significant growth in the forthcoming years.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"21 1","pages":"1"},"PeriodicalIF":2.7,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The chemokine receptor CCR5: multi-faceted hook for HIV-1.","authors":"Natacha Faivre, Christel Verollet, Fabrice Dumas","doi":"10.1186/s12977-024-00634-1","DOIUrl":"10.1186/s12977-024-00634-1","url":null,"abstract":"<p><p>Chemokines are cytokines whose primary role is cellular activation and stimulation of leukocyte migration. They perform their various functions by interacting with G protein-coupled cell surface receptors (GPCRs) and are involved in the regulation of many biological processes such as apoptosis, proliferation, angiogenesis, hematopoiesis or organogenesis. They contribute to the maintenance of the homeostasis of lymphocytes and coordinate the function of the immune system. However, chemokines and their receptors are sometimes hijacked by some pathogens to infect the host organism. For a given chemokine receptor, there is a wide structural, organizational and conformational diversity. In this review, we describe the evidence for structural variety reported for the chemokine receptor CCR5, how this variability can be exploited by HIV-1 to infect its target cells and what therapeutic solutions are currently being developed to overcome this problem.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"21 1","pages":"2"},"PeriodicalIF":2.7,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The KT Jeang retrovirology prize 2023: Thumbi Ndung'u.","authors":"Thumbi Ndung'u","doi":"10.1186/s12977-023-00632-9","DOIUrl":"10.1186/s12977-023-00632-9","url":null,"abstract":"","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"20 1","pages":"17"},"PeriodicalIF":3.3,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Murine leukemia virus (MLV) P50 protein induces cell transformation via transcriptional regulatory function.","authors":"Charbel Akkawi, Jerome Feuillard, Felipe Leon Diaz, Khalid Belkhir, Nelly Godefroy, Jean-Marie Peloponese, Marylene Mougel, Sebastien Laine","doi":"10.1186/s12977-023-00631-w","DOIUrl":"10.1186/s12977-023-00631-w","url":null,"abstract":"<p><strong>Background: </strong>The murine leukemia virus (MLV) has been a powerful model of pathogenesis for the discovery of genes involved in cancer. Its splice donor (SD')-associated retroelement (SDARE) is important for infectivity and tumorigenesis, but the mechanism remains poorly characterized. Here, we show for the first time that P50 protein, which is produced from SDARE, acts as an accessory protein that transregulates transcription and induces cell transformation.</p><p><strong>Results: </strong>By infecting cells with MLV particles containing SDARE transcript alone (lacking genomic RNA), we show that SDARE can spread to neighbouring cells as shown by the presence of P50 in infected cells. Furthermore, a role for P50 in cell transformation was demonstrated by CCK8, TUNEL and anchorage-independent growth assays. We identified the integrase domain of P50 as being responsible for transregulation of the MLV promoter using luciferase assay and RTqPCR with P50 deleted mutants. Transcriptomic analysis furthermore revealed that the expression of hundreds of cellular RNAs involved in cancerogenesis were deregulated in the presence of P50, suggesting that P50 induces carcinogenic processes via its transcriptional regulatory function.</p><p><strong>Conclusion: </strong>We propose a novel SDARE-mediated mode of propagation of the P50 accessory protein in surrounding cells. Moreover, due to its transforming properties, P50 expression could lead to a cellular and tissue microenvironment that is conducive to cancer development.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"20 1","pages":"16"},"PeriodicalIF":3.3,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10232104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primate TRIM34 is a broadly-acting, TRIM5-dependent lentiviral restriction factor.","authors":"Joy Twentyman, Anthony Khalifeh, Abby L Felton, Michael Emerman, Molly Ohainle","doi":"10.1186/s12977-023-00629-4","DOIUrl":"10.1186/s12977-023-00629-4","url":null,"abstract":"<p><p>Human immunodeficiency virus (HIV) and other lentiviruses adapt to new hosts by evolving to evade host-specific innate immune proteins that differ in sequence and often viral recognition between host species. Understanding how these host antiviral proteins, called restriction factors, constrain lentivirus replication and transmission is key to understanding the emergence of pandemic viruses like HIV-1. Human TRIM34, a paralogue of the well-characterized lentiviral restriction factor TRIM5α, was previously identified by our lab via CRISPR-Cas9 screening as a restriction factor of certain HIV and SIV capsids. Here, we show that diverse primate TRIM34 orthologues from non-human primates can restrict a range of Simian Immunodeficiency Virus (SIV) capsids including SIV_AGM-SAB, SIV_AGM-TAN and SIV_MAC capsids, which infect sabaeus monkeys, tantalus monkeys, and rhesus macaques, respectively. All primate TRIM34 orthologues tested, regardless of species of origin, were able to restrict this same subset of viral capsids. However, in all cases, this restriction also required the presence of TRIM5α. We demonstrate that TRIM5α is necessary, but not sufficient, for restriction of these capsids, and that human TRIM5α functionally interacts with TRIM34 from different species. Finally, we find that both the TRIM5α SPRY v1 loop and the TRIM34 SPRY domain are essential for TRIM34-mediated restriction. These data support a model in which TRIM34 is a broadly-conserved primate lentiviral restriction factor that acts in tandem with TRIM5α, such that together, these proteins can restrict capsids that neither can restrict alone.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"20 1","pages":"15"},"PeriodicalIF":3.3,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10212267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of PERV-C superinfection resistance using HA-tagged viruses.","authors":"Merle Flecks, Nicole Fischer, Jacomina Krijnse Locker, Ralf R Tönjes, Antonia W Godehardt","doi":"10.1186/s12977-023-00630-x","DOIUrl":"10.1186/s12977-023-00630-x","url":null,"abstract":"<p><strong>Background: </strong>Using pigs as organ donors has advanced xenotransplantation to the point that it is almost ready for clinical use. However, there is still a zoonotic risk associated with xenotransplantation, and the potential transmission of porcine endogenous retroviruses needs to be surveyed. Despite significant attempts to eliminate this risk, by the selection of PERV-C free pigs with low expression of PERV-A, -B, and by the genome-wide inactivation of PERV using CRISPR/Cas9, the impact of superinfection resistance (SIR) was not investigated. SIR is a viral trait that prevents reinfection (superinfection). For PERV, the underlying mechanism is unclear, whether and how cells, that harbor functional PERV, are protected. Using PERV-C(5683) as a reference virus, we investigated SIR in a newly developed in vitro model to pursue the mechanism and confirm its protective effect.</p><p><strong>Results: </strong>We developed three PERV-C constructs on the basis of PERV-C(5683), each of which carries a hemagglutinin tag (HA-tag) at a different position of the envelope gene (SP-HA, HA-VRA, and RPep-HA), to distinguish between primary infection and superinfection. The newly generated PERV-C(5683)-HA viruses were characterized while quantifying the viral RNA, reverse transcriptase activity, protein expression analysis, and infection studies. It was demonstrated that SP-HA and RPep-HA were comparable to PERV-C(5683), whereas HA-VRA was not replication competent. SP-HA and RPep-HA were chosen to challenge PERV-C(5683)-positive ST-IOWA cells demonstrating that PERV-C-HA viruses are not able to superinfect those cells. They do not integrate into the genome and are not expressed.</p><p><strong>Conclusions: </strong>The mechanism of SIR applies to PERV-C. The production of PERV-C particles serves as a defense mechanism from superinfection with exogenous PERV-C. It was demonstrated by newly generated PERV-C(5683)-HA clones that might be used as a cutting-edge tool. The HA-tagging of PERV-C is novel, providing a blueprint for the tagging of other human tropic PERV viruses. The tagged viruses are suitable for additional in vitro and in vivo infection studies and will contribute, to basic research on viral invasion and pathogenesis. It will maintain the virus safety of XTx.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"20 1","pages":"14"},"PeriodicalIF":3.3,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10440901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10209034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmitted/founder SHIV.D replicates in the brain, causes neuropathogenesis, and persists on combination antiretroviral therapy in rhesus macaques.","authors":"Rachel M Podgorski, Jake A Robinson, Mandy D Smith, Suvadip Mallick, Huaqing Zhao, Ronald S Veazey, Dennis L Kolson, Katharine J Bar, Tricia H Burdo","doi":"10.1186/s12977-023-00628-5","DOIUrl":"10.1186/s12977-023-00628-5","url":null,"abstract":"<p><p>A biologically relevant non-human primate (NHP) model of HIV persistence in the central nervous system (CNS) is necessary. Most current NHP/SIV models of HIV infection fail to recapitulate viral persistence in the CNS without encephalitis or fail to employ viruses that authentically represent the ongoing HIV-1 pandemic. Here, we demonstrate viral replication in the brain and neuropathogenesis after combination antiretroviral therapy (ART) in rhesus macaques (RMs) using novel macrophage-tropic transmitted/founder (TF) simian-human immunodeficiency virus SHIV.D.191,859 (SHIV.D). Quantitative immunohistochemistry (IHC) and DNA/RNAscope in situ hybridization (ISH) were performed on three brain regions from six SHIV.D-infected RMs; two necropsied while viremic, two during analytical treatment interruptions, and two on suppressive ART. We demonstrated myeloid-mediated neuroinflammation, viral replication, and proviral DNA in the brain in all animals. These results demonstrate that TF SHIV.D models native HIV-1 CNS replication, pathogenesis, and persistence on ART in rhesus macaques.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"20 1","pages":"13"},"PeriodicalIF":2.7,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10209802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence.","authors":"María José Lista,&nbsp;AnneCaroline Jousset,&nbsp;Mingpan Cheng,&nbsp;Violaine SaintAndré,&nbsp;Elouan Perrot,&nbsp;Melissa Rodrigues,&nbsp;Carmelo Di Primo,&nbsp;Danielle Gadelle,&nbsp;Elenia Toccafondi,&nbsp;Emmanuel Segeral,&nbsp;Clarisse BerliozTorrent,&nbsp;Stéphane Emiliani,&nbsp;JeanLouis Mergny,&nbsp;Marc Lavigne","doi":"10.1186/s12977-023-00627-6","DOIUrl":"https://doi.org/10.1186/s12977-023-00627-6","url":null,"abstract":"","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"20 1","pages":"12"},"PeriodicalIF":3.3,"publicationDate":"2023-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9811821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A complex network of transcription factors and epigenetic regulators involved in bovine leukemia virus transcriptional regulation.","authors":"Estelle Plant, Maxime Bellefroid, Carine Van Lint","doi":"10.1186/s12977-023-00623-w","DOIUrl":"10.1186/s12977-023-00623-w","url":null,"abstract":"<p><p>Bovine Leukemia Virus (BLV) is the etiological agent of enzootic bovine leukosis, a disease characterized by the neoplastic proliferation of B cells in cattle. While most European countries have introduced efficient eradication programs, BLV is still present worldwide and no treatment is available. A major feature of BLV infection is the viral latency, which enables the escape from the host immune system, the maintenance of a persistent infection and ultimately the tumoral development. BLV latency is a multifactorial phenomenon resulting in the silencing of viral genes due to genetic and epigenetic repressions of the viral promoter located in the 5' Long Terminal Repeat (5'LTR). However, viral miRNAs and antisense transcripts are expressed from two different proviral regions, respectively the miRNA cluster and the 3'LTR. These latter transcripts are expressed despite the viral latency affecting the 5'LTR and are increasingly considered to take part in tumoral development. In the present review, we provide a summary of the experimental evidence that has enabled to characterize the molecular mechanisms regulating each of the three BLV transcriptional units, either through cis-regulatory elements or through epigenetic modifications. Additionally, we describe the recently identified BLV miRNAs and antisense transcripts and their implications in BLV-induced tumorigenesis. Finally, we discuss the relevance of BLV as an experimental model for the closely related human T-lymphotropic virus HTLV-1.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"20 1","pages":"11"},"PeriodicalIF":2.7,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9636795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence.","authors":"María José Lista,&nbsp;Anne-Caroline Jousset,&nbsp;Mingpan Cheng,&nbsp;Violaine Saint-André,&nbsp;Elouan Perrot,&nbsp;Melissa Rodrigues,&nbsp;Carmelo Di Primo,&nbsp;Danielle Gadelle,&nbsp;Elenia Toccafondi,&nbsp;Emmanuel Segeral,&nbsp;Clarisse Berlioz-Torrent,&nbsp;Stéphane Emiliani,&nbsp;Jean-Louis Mergny,&nbsp;Marc Lavigne","doi":"10.1186/s12977-023-00625-8","DOIUrl":"https://doi.org/10.1186/s12977-023-00625-8","url":null,"abstract":"<p><strong>Background: </strong>Once integrated in the genome of infected cells, HIV-1 provirus is transcribed by the cellular transcription machinery. This process is regulated by both viral and cellular factors, which are necessary for an efficient viral replication as well as for the setting up of viral latency, leading to a repressed transcription of the integrated provirus.</p><p><strong>Results: </strong>In this study, we examined the role of two parameters in HIV-1 LTR promoter activity. We identified DNA topoisomerase1 (TOP1) to be a potent repressor of this promoter and linked this repression to its catalytic domain. Additionally, we confirmed the folding of a Guanine quadruplex (G4) structure in the HIV-1 promoter and its repressive effect. We demonstrated a direct interaction between TOP1 and this G4 structure, providing evidence of a functional relationship between the two repressive elements. Mutations abolishing G4 folding affected TOP1/G4 interaction and hindered G4-dependent inhibition of TOP1 catalytic activity in vitro. As a result, HIV-1 promoter activity was reactivated in a native chromatin environment. Lastly, we noticed an enrichment of predicted G4 sequences in the promoter of TOP1-repressed cellular genes.</p><p><strong>Conclusions: </strong>Our results demonstrate the formation of a TOP1/G4 complex on the HIV-1 LTR promoter and its repressive effect on the promoter activity. They reveal the existence of a new mechanism of TOP1/G4-dependent transcriptional repression conserved between viral and human genes. This mechanism contrasts with the known property of TOP1 as global transcriptional activator and offers new perspectives for anti-cancer and anti-viral strategies.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"20 1","pages":"10"},"PeriodicalIF":3.3,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10228017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}