Young females are at high risk of acquiring HIV-1 infections and an imbalance in the vaginal microbiome enhances susceptibility to HIV-1 infection. More insights into the underlying mechanisms could open up new strategies to prevent HIV-1 acquisition and dissemination. Here, we investigated the effect of anaerobic bacteria associated with bacterial vaginosis (BV) on HIV-1 transmission by two distinct dendritic cell (DC) subsets, that is, inflammatory monocyte-derived DCs (moDCs) and primary CD1c DCs. Notably, in contrast to other BV-associated microbiota, Prevotella timonensis enhanced uptake of HIV-1 by both moDCs and CD1c DCs and the increased uptake was independent of cellular HIV-1 (co-)receptors. Imaging flow cytometry analyses showed that HIV-1 did not co-localise with P. timonensis but was internalized into tetraspanin-positive compartments known to be involved in HIV-1 transmission. P. timonensis bacteria enhanced HIV-1 transmission by CD1c DCs, but not by moDCs, and the enhanced transmission was independent of viral infection. Our study strongly suggests that mucosal DC subsets have distinct functions in BV-associated HIV-1 susceptibility, and underscores the importance of early diagnosis and targeted treatment of vaginal dysbiosis to reduce the risk of HIV-1 acquisition.
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http://dx.doi.org/10.1002/eji.202451192 | DOI Listing |
J Immunol
February 2025
HIV Immunopathogenesis Laboratory, BEAT-HIV Delaney Collaboratory, Wistar Institute, Philadelphia, PA, United States.
Natural killer (NK) cells can efficiently mediate antibody-dependent cellular cytotoxicity (ADCC) of antibody coated target cells via the low-affinity Fc-receptor, CD16, but cannot retain antibodies over time. To increase antibody retention and facilitate targeted ADCC, we genetically modified human NK cells with the high-affinity Fc receptor, CD64, so that we could preload them with HIV-specific broadly neutralizing antibodies (BNAbs) and enhance their capacity to target HIV-infected cells via ADCC. Purified NK cells from the peripheral blood of control donors or persons living with HIV were activated with interleukin (IL)-2/IL-15/IL-21 cytokines and transduced with a lentivirus encoding CD64.
View Article and Find Full Text PDFBrief Bioinform
March 2025
Division of Microbiology, Tulane National Primate Research Center, Tulane University, Covington, LA 70433, United States.
This work aims to (1) identify microbial and metabolic alterations and (2) reveal a shift in phenylalanine production-consumption equilibrium in individuals with HIV. We conducted extensive searches in multiple databases [MEDLINE, Web of Science (including Cell Press, Oxford, HighWire, Science Direct, IOS Press, Springer Nature, PNAS, and Wiley), Google Scholar, and Embase] and selected two case-control 16S data sets (GenBank IDs: SRP039076 and EBI ID: ERP003611) for analysis. We assessed alpha and beta diversity, performed univariate tests on genus-level relative abundances, and identified significant microbiome features using random forest.
View Article and Find Full Text PDFJ Virol
March 2025
Institute of Clinical Medicine, National Yang Ming Chiao Tung University-Yangming Campus, Taipei, Taiwan.
Unlabelled: HIV-1 protease (PR) activation is triggered by Gag-Pol dimerization. We previously reported that reverse transcriptase (RT) amino acid substitution mutations resulted in p66/51RT heterodimer instability associated with impaired PR activation, and that treatment with (, an RT dimerization enhancer) increased PR activation, suggesting RT involvement. However, the contribution of RT to PR activation via the promotion of Gag-Pol dimerization has not been corroborated.
View Article and Find Full Text PDFEur J Immunol
March 2025
Department of Experimental Immunology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.
Young females are at high risk of acquiring HIV-1 infections and an imbalance in the vaginal microbiome enhances susceptibility to HIV-1 infection. More insights into the underlying mechanisms could open up new strategies to prevent HIV-1 acquisition and dissemination. Here, we investigated the effect of anaerobic bacteria associated with bacterial vaginosis (BV) on HIV-1 transmission by two distinct dendritic cell (DC) subsets, that is, inflammatory monocyte-derived DCs (moDCs) and primary CD1c DCs.
View Article and Find Full Text PDFFront Immunol
March 2025
Department of Neurology, Yale University School of Medicine, New Haven, CT, United States.
Background: Trafficking of immune cells to the central nervous system is hypothesized to facilitate HIV entry and immune-induced neuronal injury and is mediated by surface proteins such as chemokine receptors and α4 integrin. We longitudinally assessed immune cell activation and surface marker expression in cerebrospinal fluid (CSF) and blood and their relationship with CSF HIV RNA beginning during primary HIV infection (PHI) before and after antiretroviral therapy (ART).
Methods: Longitudinal paired blood and CSF were obtained in ART-naïve PHI (<12 month since infection) participants; some independently initiated ART during follow up.
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