A cohort-based study of host gene expression: tumor suppressor and innate immune/inflammatory pathways associated with the HIV reservoir size.

Autor: Ashok K Dwivedi, Germán G Gornalusse, David A Siegel, Alton Barbehenn, Cassandra Thanh, Rebecca Hoh, Kristen S Hobbs, Tony Pan, Erica A Gibson, Jeffrey Martin, Frederick Hecht, Christopher Pilcher, Jeffrey Milush, Michael P Busch, Mars Stone, Meei-Li Huang, Julieta Reppetti, Phuong M Vo, Claire N Levy, Pavitra Roychoudhury, Keith R Jerome, Florian Hladik, Timothy J Henrich, Steven G Deeks, Sulggi A Lee
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: PLoS Pathogens, Vol 19, Iss 11, p e1011114 (2023)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1011114
Popis: The major barrier to an HIV cure is the HIV reservoir: latently-infected cells that persist despite effective antiretroviral therapy (ART). There have been few cohort-based studies evaluating host genomic or transcriptomic predictors of the HIV reservoir. We performed host RNA sequencing and HIV reservoir quantification (total DNA [tDNA], unspliced RNA [usRNA], intact DNA) from peripheral CD4+ T cells from 191 ART-suppressed people with HIV (PWH). After adjusting for nadir CD4+ count, timing of ART initiation, and genetic ancestry, we identified two host genes for which higher expression was significantly associated with smaller total DNA viral reservoir size, P3H3 and NBL1, both known tumor suppressor genes. We then identified 17 host genes for which lower expression was associated with higher residual transcription (HIV usRNA). These included novel associations with membrane channel (KCNJ2, GJB2), inflammasome (IL1A, CSF3, TNFAIP5, TNFAIP6, TNFAIP9, CXCL3, CXCL10), and innate immunity (TLR7) genes (FDR-adjusted q
Databáze: Directory of Open Access Journals
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