Cellular Activation, Differentiation, and Proliferation Influence the Dynamics of Genetically Intact Proviruses Over Time.
Autor: | Horsburgh BA; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales,Australia.; Sydney Medical School, Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales,Australia., Hiener B; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales,Australia.; Sydney Medical School, Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales,Australia., Fisher K; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales,Australia.; Sydney Medical School, Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales,Australia., Lee E; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales,Australia.; Sydney Medical School, Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales,Australia., Morgan H; Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales,Australia., Eden JS; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales,Australia.; Sydney Medical School, Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales,Australia., von Stockenstrom S; Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Stockholm,Sweden., Odevall L; Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Stockholm,Sweden., Milush JM; Department of Medicine, University of California San Francisco, San Francisco, California,USA., Hoh R; Department of Medicine, University of California San Francisco, San Francisco, California,USA., Fromentin R; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM) and Department of Microbiology, Infectiology and Immunology , Université de Montréal, Montréal, Canada., Chomont N; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM) and Department of Microbiology, Infectiology and Immunology , Université de Montréal, Montréal, Canada., Hecht FM; Department of Medicine, University of California San Francisco, San Francisco, California,USA., Schlub TE; Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales,Australia., Deeks SG; Department of Medicine, University of California San Francisco, San Francisco, California,USA., Palmer S; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales,Australia.; Sydney Medical School, Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales,Australia. |
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Jazyk: | angličtina |
Zdroj: | The Journal of infectious diseases [J Infect Dis] 2022 Apr 01; Vol. 225 (7), pp. 1168-1178. |
DOI: | 10.1093/infdis/jiab291 |
Abstrakt: | Human immunodeficiency virus (HIV) persists in cells despite antiretroviral therapy; however, the influence of cellular mechanisms such as activation, differentiation, and proliferation upon the distribution of proviruses over time is unclear. To address this, we used full-length sequencing to examine proviruses within memory CD4+ T-cell subsets longitudinally in 8 participants. Over time, the odds of identifying a provirus increased in effector and decreased in transitional memory cells. In all subsets, more activated (HLA-DR-expressing) cells contained a higher frequency of intact provirus, as did more differentiated cells such as transitional and effector memory subsets. The proportion of genetically identical proviruses increased over time, indicating that cellular proliferation was maintaining the persistent reservoir; however, the number of genetically identical proviral clusters in each subset was stable. As such, key biological processes of activation, differentiation, and proliferation influence the dynamics of the HIV reservoir and must be considered during the development of any immune intervention. (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.) |
Databáze: | MEDLINE |
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