Expression of host restriction factors by memory CD4+ T cells differs between healthy donors and HIV-1 infected individuals with effective ART.

TitleExpression of host restriction factors by memory CD4+ T cells differs between healthy donors and HIV-1 infected individuals with effective ART.
Publication TypeJournal Article
Year of Publication2018
AuthorsBachtel ND, Beckerle GA, Mota T, Rougvie Mde Mulder, Raposo RAndre, R Jones B, Nixon DF, Apps R
JournalAIDS Res Hum Retroviruses
Date Published2018 Sep 10
ISSN1931-8405
Abstract

Much has been learnt from the functions of host restriction factors during acute and chronic HIV-1 infection, but far less is known about their role in HIV-1 infected individuals in which viral load is stably suppressed with anti-retroviral therapy (ART). Here transcriptional expression of 42 host restriction factors was determined for memory CD4+ T-cells sorted from 10 uninfected and 21 HIV-1 infected individuals, treated with suppressive ART and for which the viral reservoir was quantified. No significant associations were observed between restriction factor expression and HIV-1 reservoir size, quantified by measurement of HIV-1 Gag DNA using droplet digital PCR, and by measurement of replication-competent inducible virus using quantitative viral outgrowth assays. Expression of eight of the restriction factors differed significantly, and with a false discovery rate of less than 10%, between ART-suppressed and uninfected individuals. APOBEC3G, ISG15, LGALS3BP, RNASEL and MX2, were upregulated in the ART-suppressed individuals, likely due to increased levels of immune activation observed in virally suppressed compared to uninfected individuals. In contrast CDKN1A, TRIM11 and BRD4, were expressed at lower levels in ART-suppressed compared to uninfected individuals. This suggests perturbation of the CD4+ memory T cell compartment, in which a viral reservoir persists, in HIV-1 infected individuals with effective ART. Modulation of restriction factor expression, or over representation of cell subsets which intrinsically express these restriction factors at lower levels, could result in the distinct expression of restriction factors observed in treated infected individuals.

DOI10.1089/AID.2018.0162
Alternate JournalAIDS Res. Hum. Retroviruses
PubMed ID30198299