HIV transcription persists in the brain of virally suppressed people with HIV.

Autor: Jamal Eddine J; Infectious and Inflammatory Diseases, School of Health and Biomedical Sciences, RMIT University; Melbourne, Australia., Angelovich TA; Infectious and Inflammatory Diseases, School of Health and Biomedical Sciences, RMIT University; Melbourne, Australia.; Life Sciences Discipline, Burnet Institute; Melbourne, Australia.; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Zhou J; Infectious and Inflammatory Diseases, School of Health and Biomedical Sciences, RMIT University; Melbourne, Australia., Byrnes SJ; Infectious and Inflammatory Diseases, School of Health and Biomedical Sciences, RMIT University; Melbourne, Australia., Tumpach C; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Saraya N; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Chalmers E; Infectious and Inflammatory Diseases, School of Health and Biomedical Sciences, RMIT University; Melbourne, Australia., Shepherd RA; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Tan A; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Marinis S; Infectious and Inflammatory Diseases, School of Health and Biomedical Sciences, RMIT University; Melbourne, Australia., Gorry PR; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Estes JD; Infectious and Inflammatory Diseases, School of Health and Biomedical Sciences, RMIT University; Melbourne, Australia.; Vaccine & Gene Therapy Institute, Oregon Health & Science University, United States of America., Brew BJ; Peter Duncan Neurosciences Unit, Departments of Neurology and Immunology St Vincent's Hospital, Sydney, University of New South Wales and University of Notre Dame; Sydney, Australia., Lewin SR; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.; Department of Infectious Diseases, Alfred Hospital and Monash University; Melbourne, Australia.; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Telwatte S; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Roche M; Infectious and Inflammatory Diseases, School of Health and Biomedical Sciences, RMIT University; Melbourne, Australia.; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Churchill MJ; Infectious and Inflammatory Diseases, School of Health and Biomedical Sciences, RMIT University; Melbourne, Australia.; Life Sciences Discipline, Burnet Institute; Melbourne, Australia.; Departments of Microbiology and Medicine, Monash University; Melbourne, Australia.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Aug 08; Vol. 20 (8), pp. e1012446. Date of Electronic Publication: 2024 Aug 08 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012446
Abstrakt: HIV persistence in the brain is a barrier to cure, and potentially contributes to HIV-associated neurocognitive disorders. Whether HIV transcription persists in the brain despite viral suppression with antiretroviral therapy (ART) and is subject to the same blocks to transcription seen in other tissues and blood, is unclear. Here, we quantified the level of HIV transcripts in frontal cortex tissue from virally suppressed or non-virally suppressed people with HIV (PWH). HIV transcriptional profiling of frontal cortex brain tissue (and PBMCs where available) from virally suppressed (n = 11) and non-virally suppressed PWH (n = 13) was performed using digital polymerase chain reaction assays (dPCR). CD68+ myeloid cells or CD3+ T cells expressing HIV p24 protein present in frontal cortex tissue was detected using multiplex immunofluorescence imaging. Frontal cortex brain tissue from PWH had HIV TAR (n = 23/24) and Long-LTR (n = 20/24) transcripts. Completion of HIV transcription was evident in brain tissue from 12/13 non-virally suppressed PWH and from 5/11 virally suppressed PWH, with HIV p24+CD68+ cells detected in these individuals. While a block to proximal elongation was present in frontal cortex tissue from both PWH groups, this block was more extensive in virally suppressed PWH. These findings suggest that the brain is a transcriptionally active HIV reservoir in a subset of virally suppressed PWH.
Competing Interests: SRL has received investigator-initiated grant funding from Gilead, Merck and ViiV Healthcare. She has participated as a paid member of scientific advisory boards to Abivax, Immunocore, Efsam, Abbvie and Gilead.
(Copyright: © 2024 Jamal Eddine et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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