Retrovirology最新文献

{"title":"t-RNA mediates provirus deletion in HIV-infected cells.","authors":"Corrado Gurgo, Genoveffa Franchini","doi":"10.1186/s12977-025-00667-0","DOIUrl":"10.1186/s12977-025-00667-0","url":null,"abstract":"<p><strong>Background: </strong>In the early phase of HIV infection, as studied in vitro, high levels of unintegrated (both linear and circular) and integrated (provirus) forms of viral DNA are seen, and cells produce high levels of virus. In time, the level of unintegrated DNA declines, followed by a progressive decline in virus expression. Extensive studies of the proviral landscape in people living with HIV (PLWH) on antiretroviral therapy (ART) show that only about 2% of proviruses are intact; the remainder are characterized as defective and contain numerous deletions of proviral DNA segments and hypermutations. In the current study, we investigated the decline of viral expression in infected T cells in search of mechanisms involved in proviral inactivation.</p><p><strong>Results: </strong>We derived clonal lines from Jurkat cells infected with HIV MN and monitored them for viral expression over time in culture. In a subset of clones that displayed a decline in expression, we found provirus containing large deletions and the integration of a retrotranscribed molecule of tRNA^Gly adjacent to the 3'-end of the proviral DNA. We provide evidence linking the proviral deletions to the insertion of a reverse transcribed tRNA^Gly molecule and propose a mechanism for its self-primed reverse transcription.</p><p><strong>Conclusions: </strong>Large deletions of proviral DNA have been reported in PLWH on ART and attributed to errors that occurred in the synthesis of the minus strand during the reverse transcription of the viral genome. Our results support an additional mechanism for proviral deletions, mediated by tRNA^Gly, in the inactivation of the provirus.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"22 1","pages":"11"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144542035","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: HTLV-1 Japanese subgroup in Brazil: phylogenetic and migratory history.","authors":"Carolina Amianti, Larissa Melo Bandeira, Aline Pedroso Lorenz, Tayana Serpa Ortiz Tanaka, João Américo Domingos, Ana Rita Coimbra Motta-Castro","doi":"10.1186/s12977-025-00666-1","DOIUrl":"10.1186/s12977-025-00666-1","url":null,"abstract":"","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"22 1","pages":"10"},"PeriodicalIF":2.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226442","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":"Drug resistance and genetic transmission characteristics of HIV-1 CRF55_01B in people living with HIV/AIDS (PLWHA) in Henan Province, China.","authors":"Jie Ma, Jinjin Liu, Shuguang Wei, Mingjie Hou, Qingxia Zhao, Yuqi Huo","doi":"10.1186/s12977-025-00665-2","DOIUrl":"10.1186/s12977-025-00665-2","url":null,"abstract":"<p><strong>Background: </strong>Among the many CRFs, CRF55_01B was the first CRF01_AE and subtype B recombinant strain identified around 2013 among men who have sex with men (MSM) in Shenzhen, China. With rapid spreading throughout the country, CRF55_01B has attracted much attention in recent years. This study aimed to analyze its prevalence of drug resistance and transmission characteristics in people living with HIV/AIDS (PLWHA) in Henan province, China so as to pay particular attention to this group of individuals to reduce the incidence of drug resistance.</p><p><strong>Results: </strong>Two hundred and forty-five CRF55_01B-infected individuals, including 141 treatment-naïve and 104 treatment-experienced individuals, were enrolled. In treatment-naïve individuals, 6.38% (9/141) of them harboured NRTI DRMs and 19.15% (27/141) of them harboured NNRTI DRMs except V179E/D. In treatment-experienced individuals, 2.00% (2/100) harboured INSTI DRMs, 82.69% (86/104) of them harboured NRTI DRMs, and 88.46% (92/104) of them harboured NNRTI DRMs except V179E/D. The overall prevalence of ADR was 89.42% (93/104), while the prevalence of PDR was 19.86% (28/141). A total of 23 transmission clusters, accounting for 37.55% (92/245) of the total sequences, were identified. The clusters ranged in size from 2 to 19, and 15 (65.22%) had 3 or more sequences.</p><p><strong>Conclusions: </strong>High prevalence of DRMs and drug resistance were observed in CRF55_01B in both treatment-naïve and treatment-experienced individuals, particular attention should be paid to this group of individuals to reduce the incidence of drug resistance.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"22 1","pages":"9"},"PeriodicalIF":2.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182017","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":"Retroviral foamy virus gag induces parkin-dependent mitophagy.","authors":"Shanshan Wang, Tongtong Du, Jun Yan, Yingcheng Zheng, Yinglian Tang, Juejie Wu, Qian Xu, Shanshan Xu, Luo Liu, Xiong Chen, Song Han, Jun Yin, Biwen Peng, Xiaohua He, Wanhong Liu","doi":"10.1186/s12977-025-00664-3","DOIUrl":"https://doi.org/10.1186/s12977-025-00664-3","url":null,"abstract":"<p><strong>Background: </strong>Prototype foamy virus (PFV) is a complex retrovirus that can maintain latent infection for life after viral infection of the host. However, the mechanism of latent infection with PFV remains unclear. Our previous studies have shown that PFV promotes autophagy flux, but whether PFV causes mitophagy remains unclear.</p><p><strong>Results: </strong>In this study, we demonstrated that PFV infection damages mitochondria, increases mitochondria reactive oxygen species (mtROS) production, and induces mitophagy in a time-dependent manner. Further investigation revealed that PFV Gag is a crucial protein responsible for triggering mitophagy. The overexpression of Gag leads to mitochondrial damage and stimulates mitophagy in a dose-dependent manner. Additionally, overexpression of Gag activates the PINK1-Parkin signaling pathway, while the knockdown of Parkin inhibits Gag-induced mitophagy. Furthermore, Rab5a was significantly upregulated in cells overexpressed Gag, and the inhibition of Rab5a reversed the effects of Gag-induced mitophagy.</p><p><strong>Conclusions: </strong>Our data suggested that PFV can induce mitophagy and Gag induces Parkin-dependent mitophagy by upregulating Rab5a. These findings not only enhance a better understanding of the foamy virus infection mechanisms but also provide critical insights into novel virus-host cell interactions.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"22 1","pages":"7"},"PeriodicalIF":2.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009717","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":"HTLV-1 Japanese subgroup in Brazil: phylogenetic and migratory history.","authors":"Carolina Amianti, Larissa Melo Bandeira, Aline Pedroso Lorenz, Tayana Serpa Ortiz Tanaka, João Américo Domingos, Ana Rita Coimbra Motta-Castro","doi":"10.1186/s12977-025-00663-4","DOIUrl":"10.1186/s12977-025-00663-4","url":null,"abstract":"<p><strong>Background: </strong>The retrovirus Human T-lymphotropic virus type 1 is classified into different subtypes, and due to its low evolutionary rates, it can be used to explore geographic patterns of origin and dispersion of human populations. In Brazil, Transcontinental and Japanese subgroups, from the Cosmopolitan subtype, are the more common lineages, with prevalence rates notably higher among Japanese immigrants and their descendants. The study aimed to trace the history and circulation of the Japanese subgroup in Brazil using phylogenetic and populational analyses.</p><p><strong>Methods: </strong>A total of 381 HTLV-1 long terminal repeat region sequences were retrieved from the GenBank database. Phylogenetic and molecular clock analysis were performed using Maximum Likelihood and Bayesian Inference methods. A median-joining network was constructed to assess the relationships among the haplotypes of the Japanese subgroup.</p><p><strong>Results: </strong>This study found that the HTLV-1 LTR sequences from Japanese immigrants and their descendants in Brazil formed two major clades, Transcontinental (HTLV-1aTC) and Japanese (HTLV-1aJpn). Seventy-four haplotypes were identified in the haplotype network and the estimate of Japanese clade divergence dates 18,748 years ago (95% CI13,348 to 24,767 years).</p><p><strong>Conclusion: </strong>Our study corroborates the recent migratory movements as the potential mechanism for HTLV-1aJpn introduction in Brazil.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"22 1","pages":"8"},"PeriodicalIF":2.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064471","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":"Therapeutic efficacy of albuvirtide-based antiretroviral therapy in people living with HIV who have low-level viremia and non-AIDS-defining malignancies: two case reports.","authors":"Chuantiao Zhang, Tingting Xie, Yuantao Liu, Yang Cao","doi":"10.1186/s12977-025-00662-5","DOIUrl":"https://doi.org/10.1186/s12977-025-00662-5","url":null,"abstract":"<p><strong>Background: </strong>People living with HIV (PLWH) who experience low-level viremia (LLV) face unique challenges in disease management, particularly when diagnosed with concurrent malignancies. Albuvirtide (ABT), a long-acting HIV fusion inhibitor approved in China, has shown promise in clinical trials for treatment-experienced individuals. However, its efficacy in managing LLV in the context of concurrent malignancies remains under-explored.</p><p><strong>Case presentation: </strong>We report two cases of PLWH with LLV who developed non-AIDS-defining cancers(NADCs). The first individual developed lung squamous cell carcinoma, and the second was diagnosed with breast cancer. Both patients received ABT as part of their optimized antiretroviral therapy (ART) regimen during their cancer treatment course. After treatment optimization, both cases achieved viral suppression (HIV-1 RNA < 50 copies/mL) with improvements in CD4 + T cell counts. Both patients received appropriate cancer treatments according to clinical practice guidelines. The patient diagnosed with lung cancer required an adjustment to his PD-1 inhibitor monotherapy due to intolerance to chemotherapy, whereas the breast cancer patient successfully completed her planned multimodal treatment regimen.</p><p><strong>Conclusions: </strong>These cases suggest potential benefits of ABT-containing ART regimens in PLWH who have LLV and concurrent NADCs. While two cases cannot establish definitive conclusions, they highlight the need for larger studies investigating the role of ABT in this complex clinical scenario.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"22 1","pages":"6"},"PeriodicalIF":2.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012359","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":"Aberrant expression of human endogenous retrovirus K9-derived elements is associated with better clinical outcome of acute myelocytic leukemia.","authors":"Ryo Yanagiya, So Nakagawa, Makoto Onizuka, Ai Kotani","doi":"10.1186/s12977-025-00661-6","DOIUrl":"10.1186/s12977-025-00661-6","url":null,"abstract":"<p><strong>Background: </strong>Acute myelocytic leukemia (AML) is a common hematological malignancy in adults. Although several risk stratifications based on cytogenetic and molecular abnormalities are available to guide the indications for allogeneic hematopoietic cell transplantation (allo-HCT), determining optimal treatment strategies for AML remains challenging. In this study, using transcriptome datasets, we investigated the association between event-free survival (EFS) in intensively treated AML patients and the aberrant expression of endogenous viral element (EVE)-derived open reading frames (ORFs), which have been reported to be associated with the pathophysiology of various malignancies and have the potential to serve as neoantigens in specific cancers.</p><p><strong>Results: </strong>The expression levels of human endogenous retrovirus family K9 (HERVK9) ORFs were associated with EFS, independent of conventional risk stratification. Furthermore, AML cells with higher levels of HERVK9 expression exhibited enhanced antigen processing and presentation, along with increased expression of genes associated with adaptive immune responses and apoptosis, indicating that aberrant HERVK9 expression may initiate an anti-neoplastic immune response via increased antigen presentation.</p><p><strong>Conclusions: </strong>HERVK9 expression may have serve as a crucial prognostic indicator that could aid in determining the indications for upfront allo-HCT in AML patients.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"22 1","pages":"4"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754425","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":"Partial waivers: PEPFAR's 2025 funding suspension and the looming HIV/AIDS catastrophe in Sub-Saharan Africa.","authors":"Patrick Ashinze, Abba Inalegwu Owoicho, Michael Olanite","doi":"10.1186/s12977-025-00657-2","DOIUrl":"10.1186/s12977-025-00657-2","url":null,"abstract":"<p><p>Despite recent partial waivers granted by PEPFAR, the 2025 suspension of PEPFAR funding jeopardizes HIV/AIDS care for 20.6 million people, including 550,000 children, and risks reversing decades of progress in Sub-Saharan Africa (67% of global HIV burden). Immediate consequences include halted ART access, healthcare worker salary suspensions, and potential resurgence of AIDS-related deaths to 630,000 annually. Political disputes and funding misuse allegations further threaten program continuity. We urge expanded PEPFAR exemptions, rapid donor mobilization, and grassroots advocacy to avert catastrophe.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"22 1","pages":"5"},"PeriodicalIF":2.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754433","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":"Dysregulation of the tumor suppressor Menin and its target Bach2 in HTLV-1 infection.","authors":"Hiroe Sejima, Tadasuke Naito, Takuya Fukushima, Mineki Saito","doi":"10.1186/s12977-025-00660-7","DOIUrl":"10.1186/s12977-025-00660-7","url":null,"abstract":"<p><strong>Background: </strong>The tumor suppressor Menin, prone to mutations in both hereditary and sporadic endocrine tumors, along with its direct target Bach2, plays a crucial role in preventing autoimmunity by regulating CD4 + T cell senescence and maintaining cytokine homeostasis. Since human T-cell leukemia virus type 1 (HTLV-1) primarily infects CD4 + T cells, and its dysregulation contributes to both the hematological malignancy of adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we examined the involvement of the Menin-Bach2 pathway in HTLV-1 infection.</p><p><strong>Methods: </strong>The mRNA expression of menin and bach2 in HTLV-1-infected and uninfected human T-cell lines, peripheral blood mononuclear cells (PBMCs) from patients with ATL, HAM/TSP, and asymptomatic carriers were analyzed. Additionally, interactions between Menin or Bach2 and the Tax or HBZ; the subcellular localization of these proteins; the effect of knockdown of menin, tax, and HBZ genes; and the effects of interaction inhibitors between menin and its cofactor, mixed lineage leukemia (MLL), on the proliferation of HTLV-1-infected T cells were evaluated.</p><p><strong>Results: </strong>The findings were as follows: (1) In all eight HTLV-1-infected T-cell lines tested, Menin protein was expressed, whereas Bach2 expression was absent in five of them; (2) the mRNA levels of both menin and bach2 significantly decreased in PBMCs from patients with HAM/TSP and ATL; (3) Tax and HBZ each physically interacted with both Menin and Bach2; (4) knockdown of tax, but not HBZ, downregulated Bach2, but not Menin expression in HTLV-1-transformed T-cell lines MT-2 and SLB-1; (5) knockdown of menin downregulated Bach2 expression in MT-2 but not in SLB-1; (6) A Menin-MLL interaction inhibitor suppressed cell growth of MT-2 but not in SLB-1; (7) HBZ and Menin exhibited different subcellular localization between MT-2 and SLB-1.</p><p><strong>Conclusions: </strong>HTLV-1 infection alters the regulation of the Menin-Bach2 pathway, which controls cell proliferation. The Menin-MLL interaction inhibitor loses its effectiveness in suppressing cell proliferation when Menin loses control over Bach2 expression. Dysregulation of the Menin-Bach2 pathway may contribute to HTLV-1-associated disease pathogenesis.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"22 1","pages":"3"},"PeriodicalIF":2.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701381","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":"Expression of HIV from a 1-LTR circular DNA in the absence of integration.","authors":"Corrado Gurgo, Claudio Fenizia, Katherine McKinnon, Ru-Ching Hsia, Genoveffa Franchini","doi":"10.1186/s12977-025-00658-1","DOIUrl":"10.1186/s12977-025-00658-1","url":null,"abstract":"<p><strong>Background: </strong>Like all retroviruses, two kinds of viral DNA are present in the nucleus of HIV-infected cells: integrated DNA and a pool of unintegrated DNA containing linear and circular forms. For the most part, it has been difficult to examine the role of the unintegrated DNA forms in the viral life cycle in the presence of the integrated form, or to distinguish the respective contributions of the two circular DNA forms in the context of the unintegrated DNA.</p><p><strong>Results: </strong>In our approach, we constructed a 1-LTR circular form of HIV in order to study its expression in isolation from the other forms; we derived a linear genomic HIV DNA lacking the 5'-LTR (1-LTR_HIV) from a molecular clone of HIV. This linear form is transcriptionally incompetent, but via circularization becomes a transcriptionally competent 1-LTR circle. When transfected into cells lacking CD4 where neither the spread of virus nor reinfection can occur, the linear or in vitro circularized form produces a fully infectious HIV. Virus expression is stable throughout cell division as measured on a per cell basis by flow cytometry. A progressive accumulation of copies of the circular form is observed in the presence of the cell growth inhibitor aphidicolin, suggestive of episomal amplification, for which we propose a model.</p><p><strong>Conclusion: </strong>We demonstrate in this study that production of infectious virus is initiated and completed by the 1-LTR episomal form of HIV DNA in the absence of reinfection and integration. In addition, we show that the 1-LTR episomal form replicates in the absence of an origin of replication, and we propose a model for its amplification. In line with the work of others but following a different approach, we provide support for a potential role of episomal forms in HIV persistence. Our data highlight the biological complexity of HIV replication and the potential of the episomal form to contribute to the persistence of HIV.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"22 1","pages":"2"},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650087","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}