Retrovirology最新文献

{"title":"Heterologous avian system for quantitative analysis of Syncytin-1 interaction with ASCT2 receptor.","authors":"Kryštof Štafl,&nbsp;Martin Trávníček,&nbsp;Dana Kučerová,&nbsp;Ľubomíra Pecnová,&nbsp;Veronika Krchlíková,&nbsp;Eliška Gáliková,&nbsp;Volodymyr Stepanets,&nbsp;Jiří Hejnar,&nbsp;Kateřina Trejbalová","doi":"10.1186/s12977-021-00558-0","DOIUrl":"https://doi.org/10.1186/s12977-021-00558-0","url":null,"abstract":"<p><strong>Background: </strong>Human Syncytin-1 is a placentally-expressed cell surface glycoprotein of retroviral origin. After interaction with ASCT2, its cellular receptor, Syncytin-1 triggers cell-cell fusion and formation of a multinuclear syncytiotrophoblast layer of the placenta. The ASCT2 receptor is a multi-spanning membrane protein containing a protruding extracellular part called region C, which has been suggested to be a retrovirus docking site. Precise identification of the interaction site between ASCT2 and Syncytin-1 is challenging due to the complex structure of ASCT2 protein and the background of endogenous ASCT2 gene in the mammalian genome. Chicken cells lack the endogenous background and, therefore, can be used to set up a system with surrogate expression of the ASCT2 receptor.</p><p><strong>Results: </strong>We have established a retroviral heterologous chicken system for rapid and reliable assessment of ectopic human ASCT2 protein expression. Our dual-fluorescence system proved successful for large-scale screening of mutant ASCT2 proteins. Using this system, we demonstrated that progressive deletion of region C substantially decreased the amount of ASCT2 protein. In addition, we implemented quantitative assays to determine the interaction of ASCT2 with Syncytin-1 at multiple levels, which included binding of the soluble form of Syncytin-1 to ASCT2 on the cell surface and a luciferase-based assay to evaluate cell-cell fusions that were triggered by Syncytin-1. Finally, we restored the envelope function of Syncytin-1 in a replication-competent retrovirus and assessed the infection of chicken cells expressing human ASCT2 by chimeric Syncytin-1-enveloped virus. The results of the quantitative assays showed that deletion of the protruding region C did not abolish the interaction of ASCT2 with Syncytin-1.</p><p><strong>Conclusions: </strong>We present here a heterologous chicken system for effective assessment of the expression of transmembrane ASCT2 protein and its interaction with Syncytin-1. The system profits from the absence of endogenous ASCT2 background and implements the quantitative assays to determine the ASCT2-Syncytin-1 interaction at several levels. Using this system, we demonstrated that the protruding region C was essential for ASCT2 protein expression, but surprisingly, not for the interaction with Syncytin-1 glycoprotein.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12977-021-00558-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39029037","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":"Advancing our understanding of HIV co-infections and neurological disease using the humanized mouse.","authors":"Janice J Endsley, Matthew B Huante, Kubra F Naqvi, Benjamin B Gelman, Mark A Endsley","doi":"10.1186/s12977-021-00559-z","DOIUrl":"10.1186/s12977-021-00559-z","url":null,"abstract":"<p><p>Humanized mice have become an important workhorse model for HIV research. Advances that enabled development of a human immune system in immune deficient mouse strains have aided new basic research in HIV pathogenesis and immune dysfunction. The small animal features facilitate development of clinical interventions that are difficult to study in clinical cohorts, and avoid the high cost and regulatory burdens of using non-human primates. The model also overcomes the host restriction of HIV for human immune cells which limits discovery and translational research related to important co-infections of people living with HIV. In this review we emphasize recent advances in modeling bacterial and viral co-infections in the setting of HIV in humanized mice, especially neurological disease, and Mycobacterium tuberculosis and HIV co-infections. Applications of current and future co-infection models to address important clinical and research questions are further discussed.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39237146","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":"Humanized Mice for Infectious and Neurodegenerative disorders.","authors":"Prasanta K Dash, Santhi Gorantla, Larisa Poluektova, Mahmudul Hasan, Emiko Waight, Chen Zhang, Milica Markovic, Benson Edagwa, Jatin Machhi, Katherine E Olson, Xinglong Wang, R Lee Mosley, Bhavesh Kevadiya, Howard E Gendelman","doi":"10.1186/s12977-021-00557-1","DOIUrl":"10.1186/s12977-021-00557-1","url":null,"abstract":"<p><p>Humanized mice model human disease and as such are used commonly for research studies of infectious, degenerative and cancer disorders. Recent models also reflect hematopoiesis, natural immunity, neurobiology, and molecular pathways that influence disease pathobiology. A spectrum of immunodeficient mouse strains permit long-lived human progenitor cell engraftments. The presence of both innate and adaptive immunity enables high levels of human hematolymphoid reconstitution with cell susceptibility to a broad range of microbial infections. These mice also facilitate investigations of human pathobiology, natural disease processes and therapeutic efficacy in a broad spectrum of human disorders. However, a bridge between humans and mice requires a complete understanding of pathogen dose, co-morbidities, disease progression, environment, and genetics which can be mirrored in these mice. These must be considered for understanding of microbial susceptibility, prevention, and disease progression. With known common limitations for access to human tissues, evaluation of metabolic and physiological changes and limitations in large animal numbers, studies in mice prove important in planning human clinical trials. To these ends, this review serves to outline how humanized mice can be used in viral and pharmacologic research emphasizing both current and future studies of viral and neurodegenerative diseases. In all, humanized mouse provides cost-effective, high throughput studies of infection or degeneration in natural pathogen host cells, and the ability to test transmission and eradication of disease.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2021-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9762126","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":"Neutralization diversity of HIV-1 Indian subtype C envelopes obtained from cross sectional and followed up individuals against broadly neutralizing monoclonal antibodies having distinct gp120 specificities.","authors":"Ranajoy Mullick, Jyoti Sutar, Nitin Hingankar, Suprit Deshpande, Madhuri Thakar, Seema Sahay, Rajesh P Ringe, Sampurna Mukhopadhyay, Ajit Patil, Shubhangi Bichare, Kailapuri G Murugavel, Aylur K Srikrishnan, Rajat Goyal, Devin Sok, Jayanta Bhattacharya","doi":"10.1186/s12977-021-00556-2","DOIUrl":"10.1186/s12977-021-00556-2","url":null,"abstract":"<p><strong>Background: </strong>The potential use of the broadly neutralizing monoclonal antibodies (bnAbs) towards prophylaxis and treatment to HIV-1 is currently being explored. While a number of promising bnAbs have been discovered and a few of them have progressed towards clinical development, their extent of neutralization coverage with respect to global HIV-1 variants given the existence of genetically distinct subtypes and recombinants circulating globally is not clearly known. In the present study, we examined the variation in the neutralization susceptibility of pseudoviruses expressing 71 full length primary HIV-1 subtype C envs obtained from limited cross-sectional individuals over different time points against four bnAbs that target gp120 with distinct specificities: VRC01, CAP256-VRC26.25, PGDM1400 and PGT121.</p><p><strong>Results: </strong>We found significant variations in the susceptibility of Indian clade C to these four bnAbs. These variations were found to be distinct to that observed in African subtype C based on the existing datasets and concordant with their sequence diversity. Trend analysis indicated an increasing neutralization resistance observed over time with CAP25-VRC26.25, PGDM1400 and PGT121 when tested on pseudoviruses expressing envs obtained from 1999 to 2016. However, inconsistent trend in neutralization susceptibility was observed, when pseudoviruses expressing envs obtained from three followed up individuals were examined. Finally, through predictive analysis of the 98 Indian subtype C including those assessed in the present study by employing additive model implemented in CombiNAber ( http://www.hiv.lanl.gov ), we observed two possibilities where combinations of three bnAbs (VRC01/CAP56-VRC26.25/PGT121 and PGDM1400/CAP256-VRC26.25/PGT121) could achieve near 100% neutralization coverage.</p><p><strong>Conclusions: </strong>Our findings not only indicate disparate intra-clade C genetic vis-à-vis neutralization diversities but also warrant the need for more comprehensive study using additional isolates towards comparing inter and intra-clade neutralization diversities which will be necessary for selecting the bnAb combinations suitable for optimal coverage of the region-specific HIV-1 circulating subtypes. Expanding these efforts is imperative for designing efficacious bnAb based intervention strategies for India as well as subtype C in general.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38983445","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":"Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa.","authors":"Omotayo Farinre, Kamini Gounder, Tarylee Reddy, Marcel Tongo, Jonathan Hare, Beth Chaplin, Jill Gilmour, Phyllis Kanki, Jaclyn K Mann, Thumbi Ndung'u","doi":"10.1186/s12977-021-00554-4","DOIUrl":"10.1186/s12977-021-00554-4","url":null,"abstract":"<p><strong>Background: </strong>The HIV-1 epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence. Subtype-specific differences in disease progression rate and transmission efficiency have been reported, but the underlying biological mechanisms have not been fully characterized. Here, we tested the hypothesis that the subtypes prevalent in the East Africa, where adult prevalence rate is higher, have lower viral replication capacity (VRC) than their West African counterparts where adult prevalence rates are lower.</p><p><strong>Results: </strong>Gag-protease sequencing was performed on 213 and 160 antiretroviral-naïve chronically infected participants from West and East Africa respectively and bioinformatic tools were used to infer subtypes and recombination patterns. VRC of patient-derived gag-protease chimeric viruses from West (n = 178) and East (n = 114) Africa were determined using a green fluorescent protein reporter-based cell assay. Subtype and regional differences in VRC and amino acid variants impacting VRC were identified by statistical methods. CRF02_AG (65%, n = 139), other recombinants (14%, n = 30) and pure subtypes (21%, n = 44) were identified in West Africa. Subtypes A1 (64%, n = 103), D (22%, n = 35), or recombinants (14%, n = 22) were identified in East Africa. Viruses from West Africa had significantly higher VRC compared to those from East Africa (p < 0.0001), with subtype-specific differences found among strains within West and East Africa (p < 0.0001). Recombination patterns showed a preference for subtypes D, G or J rather than subtype A in the p6 region of gag, with evidence that subtype-specific differences in this region impact VRC. Furthermore, the Gag A83V polymorphism was associated with reduced VRC in CRF02_AG. HLA-A*23:01 (p = 0.0014) and HLA-C*07:01 (p = 0.002) were associated with lower VRC in subtype A infected individuals from East Africa.</p><p><strong>Conclusions: </strong>Although prevalent viruses from West Africa displayed higher VRC than those from East Africa consistent with the hypothesis that lower VRC is associated with higher population prevalence, the predominant CRF02_AG strain in West Africa displayed higher VRC than other prevalent strains suggesting that VRC alone does not explain population prevalence. The study identified viral and host genetic determinants of virus replication capacity for HIV-1 CRF02_AG and subtype A respectively, which may have relevance for vaccine strategies.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38952995","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":"Falling fowl of the chicken reference genome: pitfalls of studying polymorphic endogenous retroviruses.","authors":"Andrew S Mason","doi":"10.1186/s12977-021-00555-3","DOIUrl":"10.1186/s12977-021-00555-3","url":null,"abstract":"<p><p>High quality reference genomes have facilitated the study of endogenous retroviruses (ERVs). However, there are an increasing number of published works which assume the ERVs in reference genomes are universal; even those of evolutionarily recent integrations. Consequently, these studies fail to properly characterise polymorphic ERVs, and even propose biological functions for ERVs that may not actually be present in the genomes of interest. Here, I outline the pitfalls of three studies of chicken endogenous Avian Leukosis Viruses (ALVEs or \"ev genes\": the \"original\" ERVs), all confounded by the assumption that the reference genome provides a representative ALVE baseline.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38893322","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 single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors.","authors":"Dibya Ghimire,&nbsp;Yuvraj Kc,&nbsp;Uddhav Timilsina,&nbsp;Kriti Goel,&nbsp;T J Nitz,&nbsp;Carl T Wild,&nbsp;Ritu Gaur","doi":"10.1186/s12977-021-00553-5","DOIUrl":"https://doi.org/10.1186/s12977-021-00553-5","url":null,"abstract":"<p><strong>Background: </strong>Maturation inhibitors (MIs) potently block HIV-1 maturation by inhibiting the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a highly efficacious first-in-class MI against HIV-1 subtype B isolates, elicited sub-optimal efficacy in clinical trials due to polymorphisms in the CA-SP1 region of the Gag protein (SP1:V7A). HIV-1 subtype C inherently contains this polymorphism thus conferring BVM resistance, however it displayed sensitivity to second generation BVM analogs.</p><p><strong>Results: </strong>In this study, we have assessed the efficacy of three novel second-generation MIs (BVM analogs: CV-8611, CV-8612, CV-8613) against HIV-1 subtype B and C isolates. The BVM analogs were potent inhibitors of both HIV-1 subtype B (NL4-3) and subtype C (K3016) viruses. Serial passaging of the subtype C, K3016 virus strain in the presence of BVM analogs led to identification of two mutant viruses-Gag SP1:A1V and CA:I201V. While the SP1:A1V mutant was resistant to the MIs, the CA:I120V mutant displayed partial resistance and a MI-dependent phenotype. Further analysis of the activity of the BVM analogs against two additional HIV-1 subtype C strains, IndieC1 and ZM247 revealed that they had reduced sensitivity as compared to K3016. Sequence analysis of the three viruses identified two polymorphisms at SP1 residues 9 and 10 (K3016: N9, G10; IndieC1/ZM247: S9, T10). The N9S and S9N mutants had no change in MI-sensitivity. On the other hand, replacing glycine at residue 10 with threonine in K3016 reduced its MI sensitivity whereas introducing glycine at SP1 10 in place of threonine in IndieC1 and ZM247 significantly enhanced their MI sensitivity. Thus, the specific glycine residue 10 of SP1 in the HIV-1 subtype C viruses determined sensitivity towards BVM analogs.</p><p><strong>Conclusions: </strong>We have identified an association of a specific glycine at position 10 of Gag-SP1 with an MI susceptible phenotype of HIV-1 subtype C viruses. Our findings have highlighted that HIV-1 subtype C viruses, which were inherently resistant to BVM, may also be similarly predisposed to exhibit a significant degree of resistance to second-generation BVM analogs. Our work has strongly suggested that genetic differences between HIV-1 subtypes may produce variable MI sensitivity that needs to be considered in the development of novel, potent, broadly-active MIs.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25577223","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":"Memoriam for Renaud Mahieux.","authors":"Fatah Kashanchi,&nbsp;Ali Bazarbachi,&nbsp;Antoine Gessain","doi":"10.1186/s12977-021-00551-7","DOIUrl":"https://doi.org/10.1186/s12977-021-00551-7","url":null,"abstract":"","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12977-021-00551-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25488158","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":"Elevated levels of inflammatory plasma biomarkers are associated with risk of HIV infection.","authors":"Samantha McInally,&nbsp;Kristin Wall,&nbsp;Tianwei Yu,&nbsp;Rabindra Tirouvanziam,&nbsp;William Kilembe,&nbsp;Jill Gilmour,&nbsp;Susan A Allen,&nbsp;Eric Hunter","doi":"10.1186/s12977-021-00552-6","DOIUrl":"https://doi.org/10.1186/s12977-021-00552-6","url":null,"abstract":"<p><strong>Background: </strong>To determine if individuals, from HIV-1 serodiscordant couple cohorts from Rwanda and Zambia, who become HIV-positive have a distinct inflammatory biomarker profile compared to individuals who remain HIV-negative, we compared levels of biomarkers in plasma of HIV-negative individuals who either seroconverted (pre-infection) and became HIV-positive or remained HIV-negative (uninfected).</p><p><strong>Results: </strong>We observed that individuals in the combined cohort, as well as those in the individual country cohorts, who later became HIV-1 infected had significantly higher baseline levels of multiple inflammatory cytokines/chemokines compared to individuals who remained HIV-negative. Genital inflammation/ulceration or schistosome infections were not associated with this elevated profile. Defined levels of ITAC and IL-7 were significant predictors of later HIV acquisition in ROC predictive analyses, whereas the classical Th1 and Th2 inflammatory cytokines such as IL-12 and interferon-γ or IL-4, IL-5 and Il-13 were not.</p><p><strong>Conclusions: </strong>Overall, the data show a significant association between increased plasma biomarkers linked to inflammation and immune activation and HIV acquisition and suggests that pre-existing conditions that increase systemic biomarkers represent a factor for increased risk of HIV infection.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12977-021-00552-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25487873","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":"Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread.","authors":"Daniel O Pinto, Sarah Al Sharif, Gifty Mensah, Maria Cowen, Pooja Khatkar, James Erickson, Heather Branscome, Thomas Lattanze, Catherine DeMarino, Farhang Alem, Ruben Magni, Weidong Zhou, Sandrine Alais, Hélène Dutartre, Nazira El-Hage, Renaud Mahieux, Lance A Liotta, Fatah Kashanchi","doi":"10.1186/s12977-021-00550-8","DOIUrl":"10.1186/s12977-021-00550-8","url":null,"abstract":"<p><strong>Background: </strong>The Human T-cell Lymphotropic Virus Type-1 (HTLV-1) is a blood-borne pathogen and etiological agent of Adult T-cell Leukemia/Lymphoma (ATLL) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HTLV-1 has currently infected up to 10 million globally with highly endemic areas in Japan, Africa, the Caribbean and South America. We have previously shown that Extracellular Vesicles (EVs) enhance HTLV-1 transmission by promoting cell-cell contact.</p><p><strong>Results: </strong>Here, we separated EVs into subpopulations using differential ultracentrifugation (DUC) at speeds of 2 k (2000×g), 10 k (10,000×g), and 100 k (100,000×g) from infected cell supernatants. Proteomic analysis revealed that EVs contain the highest viral/host protein abundance in the 2 k subpopulation (2 k > 10 k > 100 k). The 2 k and 10 k populations contained viral proteins (i.e., p19 and Tax), and autophagy proteins (i.e., LC3 and p62) suggesting presence of autophagosomes as well as core histones. Interestingly, the use of 2 k EVs in an angiogenesis assay (mesenchymal stem cells + endothelial cells) caused deterioration of vascular-like-tubules. Cells commonly associated with the neurovascular unit (i.e., astrocytes, neurons, and macrophages) in the blood-brain barrier (BBB) showed that HTLV-1 EVs may induce expression of cytokines involved in migration (i.e., IL-8; 100 k > 2 k > 10 k) from astrocytes and monocyte-derived macrophages (i.e., IL-8; 2 k > 10 k). Finally, we found that EVs were able to promote cell-cell contact and viral transmission in monocytic cell-derived dendritic cell. The EVs from both 2 k and 10 k increased HTLV-1 spread in a humanized mouse model, as evidenced by an increase in proviral DNA and RNA in the Blood, Lymph Node, and Spleen.</p><p><strong>Conclusions: </strong>Altogether, these data suggest that various EV subpopulations induce cytokine expression, tissue damage, and viral spread.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2021-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25397775","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}