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Hierarchical Clustering and Trajectory Analyses Reveal Viremia-Independent B-Cell Perturbations in HIV-2 Infection
Department of Laboratory Medicine, Lund University, Lund, Sweden.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands.
Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
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2022 (English)In: Cells, E-ISSN 2073-4409, Vol. 11, no 19, article id 3142Article in journal (Refereed) Published
Abstract [en]

Time to AIDS in HIV-2 infection is approximately twice as long compared to in HIV-1 infection. Despite reduced viremia, HIV-2-infected individuals display signs of chronic immune activation. In HIV-1-infected individuals, B-cell hyperactivation is driven by continuous antigen exposure. However, the contribution of viremia to B-cell perturbations in HIV-2-infected individuals remains largely unexplored. Here, we used polychromatic flow cytometry, consensus hierarchical clustering and pseudotime trajectory inference to characterize B-cells in HIV-1- or HIV-2-infected and in HIV seronegative individuals. We observed increased frequencies of clusters containing hyperactivated T-bethighCD95highCD27int and proliferating T-bet+CD95highCD27+CD71+ memory B-cells in viremic HIV-1 (p < 0.001 and p < 0.001, respectively), viremic HIV-2 (p < 0.001 and p = 0.014, respectively) and in treatment-naïve aviremic HIV-2 (p = 0.004 and p = 0.020, respectively)-infected individuals, compared to seronegative individuals. In contrast, these expansions were not observed in successfully treated HIV-1-infected individuals. Finally, pseudotime trajectory inference showed that T-bet-expressing hyperactivated and proliferating memory B-cell populations were located at the terminal end of two trajectories, in both HIV-1 and HIV-2 infections. As the treatment-naïve aviremic HIV-2-infected individuals, but not the successfully ART-treated HIV-1-infected individuals, showed B-cell perturbations, our data suggest that aviremic HIV-2-infected individuals would also benefit from antiretroviral treatment.

Place, publisher, year, edition, pages
MDPI, 2022. Vol. 11, no 19, article id 3142
Keywords [en]
B-cell phenotype, CD95, HIV-1, HIV-2, immune perturbations, T-bet, viremia
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-203257DOI: 10.3390/cells11193142ISI: 000866660900001PubMedID: 36231103Scopus ID: 2-s2.0-85139931412OAI: oai:DiVA.org:umu-203257DiVA, id: diva2:1727725
Funder
Swedish Research Council, 2016-02285Swedish Research Council, 2019-01439Swedish Research Council, 2020-06262Swedish Research Council, 2020-06235Swedish Fund for Research Without Animal Experiments, N2019-0009Swedish Fund for Research Without Animal Experiments, F2021-0010Available from: 2023-01-17 Created: 2023-01-17 Last updated: 2023-01-17Bibliographically approved

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Kerkman, PriscillaForsell, Mattias N. E.

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