Retrovirology最新文献

Background: 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.

Results: 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.

Conclusions: 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.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: Our study corroborates the recent migratory movements as the potential mechanism for HTLV-1aJpn introduction in Brazil.

Background: 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.

Case presentation: 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.

Conclusions: 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.

Background: 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.

Results: 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.

Conclusions: HERVK9 expression may have serve as a crucial prognostic indicator that could aid in determining the indications for upfront allo-HCT in AML patients.

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.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Background: 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.

Results: 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.

Conclusion: 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.

Background: 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).

Materials and methods: 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).

Results: 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).

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: The result of this study suggests that BLV infection is statistically associated with Breast cancer.