Retrovirology最新文献

{"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}

{"title":"Correction: 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/s12977-025-00659-0","DOIUrl":"10.1186/s12977-025-00659-0","url":null,"abstract":"","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"22 1","pages":"1"},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524284","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":"Declining trend of HTLV-1 among organ/ tissue donors in Iranian Tissue Bank between 2014-2021.","authors":"Arash Letafati, Sayed Hamidreza Mozhgani, Mehdi Norouzi, Amir Aboofazeli, Zahra Taghiabadi, Negar Zafarian, Saba Seyedi, Elnaz Mohammad Jaberi, Sedigheh Poursaleh, Maryam Karami, Sheida Sarrafzadeh, Ahmadreza Sadeghi","doi":"10.1186/s12977-024-00656-9","DOIUrl":"10.1186/s12977-024-00656-9","url":null,"abstract":"<p><strong>Background: </strong>Human T-cell Lymphotropic Virus type-1 (HTLV-1) infection is associated with serious disorders, including Adult T-cell Leukemia/Lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In addition to sexual, vertical, parenteral, and blood transfusion, organ/tissue transplantation is considered as a transmission route of HTLV infection. Given the substantial risk of HTLV-1 transmission and the subsequent development of HAM/TSP (approximately 40%) in kidney transplant recipients, pre-transplant donor screening is crucial. The present study aimed to investigate the prevalence of HTLV-1 in potential organ/tissue donors referred to the Iranian Tissue Bank and Research Center (ITBRC).</p><p><strong>Materials and methods: </strong>The study population was potential organ and/or tissue donors referred to ITBRC between 2014 and 2021, including two groups of brain death (potential donors of organs and/or tissues) and circulatory death donors (potential tissue donors from Iranian Legal Medicine Organization). Initial screening was performed using enzyme-linked immunosorbent assay (ELISA), and positive cases were confirmed for HTLV-1 infection with polymerase chain reaction (PCR).</p><p><strong>Results: </strong>111 out of 3,814 donors were positive for HTLV-1 (3%). The rate of positive tests between 2014 and 2017 was 6%, which was significantly higher than the positive tests percentage between 2017 and 2021 with 0.5% (P-value < 0.001). The rate of test positivity in females was 4% compared to 2% in males (P-value = 0.001). Furthermore, individuals diagnosed with brain death exhibited a significantly lower likelihood of HTLV-1 infection (0.2%) compared to cases with circulatory death (4%) (P-value < 0.001).</p><p><strong>Conclusion: </strong>Considering the contraindication of organ/tissue donation from donors with HTLV-1 positive test, these findings give an insight into the prevalence of HTLV-1 among potential organ/tissue donors in Iran. Moreover, the higher prevalence of HTLV-1 infection in circulatory death donors from Iranian Legal Medicine Organization urges for cautious evaluation in these donors.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"21 1","pages":"22"},"PeriodicalIF":2.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847691","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":"Bovine leukemia virus (BLV) and risk of breast cancer; a systematic review and meta-analysis.","authors":"Fateme Saeedi-Moghaddam, Mahdi Mohammaditabar, Sayed-Hamidreza Mozhgani","doi":"10.1186/s12977-024-00653-y","DOIUrl":"10.1186/s12977-024-00653-y","url":null,"abstract":"<p><strong>Background: </strong>The role of viruses in the development of breast cancer has been a subject of debate and extensive research over the past few decades. Several studies have examined the association between Bovine leukemia virus (BLV) infection and the risk of developing breast cancer; however, their findings have yielded inconsistent results. To address this uncertainty, the purpose of the present study was to conduct a systematic review and meta-analysis to determine any potential association between BLV and breast cancer.</p><p><strong>Methods: </strong>The literature search was performed by finding related articles from PubMed, Web of Science, Scopus, EMBASE, and ScienceDirect databases. Statistical analysis was conducted using the meta package in R Studio and Review Manager 5.1. The I² test was used to assess between-study heterogeneity. The Mantel-Haenszel method calculated the pooled odds ratio and its 95% confidence interval. Studies were divided into subgroups for comparison.</p><p><strong>Results: </strong>The literature search identified a total of 17 studies that were deemed suitable for inclusion in the systematic review. Out of these 17 studies, 12 were used in the subsequent meta-analysis. Combining the data from these eligible studies, we calculated the pooled multi-factor adjusted odds ratio (OR) and a 95% confidence interval (CI). Considering the heterogeneity observed across the studies, the result obtained using the fixed effects model was 2.12 (1.77, 2.54). However, upon removing the six studies that contributed significantly to the heterogeneity, the pooled OR with a 95% CI was recalculated to be 3.92 (2.98, 5.16).</p><p><strong>Conclusion: </strong>The result of this study suggests that BLV infection is statistically associated with Breast cancer.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"21 1","pages":"20"},"PeriodicalIF":2.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771994","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":"Exploring potential associations between the human microbiota and reservoir of latent HIV.","authors":"Nel Marín-Sánchez, Roger Paredes, Alessandra Borgognone","doi":"10.1186/s12977-024-00655-w","DOIUrl":"10.1186/s12977-024-00655-w","url":null,"abstract":"<p><strong>Background: </strong>The rapid establishment and persistence of latent HIV-1 reservoirs is one of the main obstacles towards an HIV cure. While antiretroviral therapy supresses viral replication, it does not eradicate the latent reservoir of HIV-1-infected cells. Recent evidence suggests that the human microbiome, particularly the gut microbiome, may have the potential to modulate the HIV-1 reservoir. However, literature is limited and the exact mechanisms underlying the role of the microbiome in HIV immunity and potential regulation of the viral reservoir remain poorly understood.</p><p><strong>Results: </strong>Here, we review updated knowledge on the associations between the human microbiome and HIV reservoir across different anatomical sites, including the gut, the lungs and blood. We provide an overview of the predominant taxa associated with prominent microbiome changes in the context of HIV infection. Based on the current evidence, we summarize the main study findings, with specific focus on consistent bacterial and related byproduct associations. Specifically, we address the contribution of immune activation and inflammatory signatures on HIV-1 persistence. Furthermore, we discuss possible scenarios by which bacterial-associated inflammatory mediators, related metabolites and host immune signatures may modulate the HIV reservoir size. Finally, we speculate on potential implications of microbiome-based therapeutics for future HIV-1 cure strategies, highlighting challenges and limitations inherent in this research field.</p><p><strong>Conclusions: </strong>Despite recent advances, this review underscores the need for further research to deepen the understanding of the complex interplay between the human microbiome and HIV reservoir. Further integrative multi-omics assessments and functional studies are crucial to test the outlined hypothesis and to identify potential therapeutic targets ultimately able to achieve an effective cure for HIV.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"21 1","pages":"21"},"PeriodicalIF":2.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755387","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":"Exceptional molecular and coreceptor-requirement properties of molecular clones isolated from an human immunodeficiency virus Type-1 subtype C infection.","authors":"Prasanta K Dash, Nagadenahalli B Siddappa, Asokan Mangaiarkarasi, Aruna V Mahendarkar, Padmanabhan Roshan, Krishnamurthy Kumar Anand, Anita Mahadevan, Parthasarathy Satishchandra, Susarla K Shankar, Vinayaka R Prasad, Udaykumar Ranga","doi":"10.1186/s12977-024-00654-x","DOIUrl":"10.1186/s12977-024-00654-x","url":null,"abstract":"","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"21 1","pages":"19"},"PeriodicalIF":2.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605504","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 infection in urban population from Mato Grosso do Sul, Central Brazil.","authors":"Carolina Amianti, Larissa Melo Bandeira, Wesley Marcio Cardoso, Andréia Souza Pinto da Silva, Milena da Silva de Jesus, Rodrigo Ibañez, Felipe Bonfim Freitas, Silvia Naomi de Oliveira Uehara, Izaura Maria Vieira Cayres Vallinoto, Antonio Carlos Rosário Vallinoto, Ana Rita Coimbra Motta-Castro","doi":"10.1186/s12977-024-00650-1","DOIUrl":"10.1186/s12977-024-00650-1","url":null,"abstract":"<p><strong>Background: </strong>Brazil has the highest number of HTLV-1 infection in Latin America, with around one million cases spread unevenly across regions. However, there is a limited number of studies on this infection in the general population. This cross-sectional study aimed to estimate the prevalence of HTLV as well as identify types, and subtypes of HTLV among the urban population of Campo Grande, capital of Mato Grosso do Sul state (MS).</p><p><strong>Results: </strong>Between July 2023 and March 2024, all information was obtained from self-reported interviews, and blood samples were collected and screened for anti-HTLV-1/2 by immunoassay and confirmed using the immunoblot method. The proviral DNA of HTLV-1/2 in positive samples was quantified by real-time PCR (qPCR) and genotyped by nucleotide sequencing (Sanger's method). The study enrolled 611 participants, with the majority being women (90.54%), mixed race (46.32%), heterosexual (87.64%), and with a median age of 39 years. The prevalence rate of anti-HTLV-1 infection was 0.82% (CI 95% 0.34-1.96). All positive samples (n = 5) were identified as belonging to the Cosmopolitan subtype, one belonging to Japanese and four to Transcontinental subgroups. Among the five positive individuals, two presented symptoms associated with HTLV-1 infection.</p><p><strong>Conclusion: </strong>This study highlights an intermediate prevalence of HTLV-1 in the urban population of Campo Grande, Mato Grosso do Sul, and provides epidemiological information that could help bridge the gaps in the distribution of HTLV in the general population. Also, medical care was provided for individuals presenting clinical manifestations who were previously unaware of their serological status.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"21 1","pages":"18"},"PeriodicalIF":2.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584189","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}