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HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells.

Identifieur interne : 000D45 ( PubMed/Corpus ); précédent : 000D44; suivant : 000D46

HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells.

Auteurs : Yin Xu ; Chansavath Phetsouphanh ; Kazuo Suzuki ; Anu Aggrawal ; Stephanie Graff-Dubois ; Michael Roche ; Michelle Bailey ; Sheilajen Alcantara ; Kieran Cashin ; Rahuram Sivasubramaniam ; Kersten K. Koelsch ; Brigitte Autran ; Richard Harvey ; Paul R. Gorry ; Arnaud Moris ; David A. Cooper ; Stuart Turville ; Stephen J. Kent ; Anthony D. Kelleher ; John Zaunders

Source :

RBID : pubmed:28484447

Abstract

T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4(+) T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells.

DOI: 10.3389/fimmu.2017.00376
PubMed: 28484447

Links to Exploration step

pubmed:28484447

Le document en format XML

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<div type="abstract" xml:lang="en">T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4(+) T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells.</div>
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<AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4(+) T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells.</AbstractText>
<AbstractText Label="METHODOLOGY" NlmCategory="METHODS">Tfh and other CD4(+) T cell subsets from macaque lymph nodes and spleens, splenic Tfh from HIV(+) subjects, and tonsillar Tfh from HIV-uninfected subjects were isolated by cell sorting prior to cell surface and molecular characterization. HIV proviral gp120 sequences were submitted to genotypic and phenotypic tropism assays. Entry of CCR5- and CXCR4-using viruses into Tfh from uninfected tonsillar tissue was measured using a fusion assay.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">Phylogenetic analysis, genotypic, and phenotypic analysis showed that splenic Tfh cells from chronic HIV(+) subjects were predominantly infected with CCR5-using viruses. In macaques, purified CCR5(+)PD-1(intermediate(int)+) memory CD4(+) T cells were shown to include pre-Tfh cells capable of differentiating in vitro to Tfh by upregulation of PD-1 and Bcl6, confirmed by qRT-PCR and single-cell multiplex PCR. Infected PD-1(int) cells survive, carry SIV provirus, and differentiate into PD-1(hi) Tfh after T cell receptor stimulation, suggesting a pathway for SIV infection of Tfh. In addition, a small subset of macaque and human PD-1(hi) Tfh can express low levels of CCR5, which makes them susceptible to infection. Fusion assays demonstrated CCR5-using HIV-1 entry into CCR5(+) Tfh and pre-Tfh cells from human tonsils.</AbstractText>
<AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">The major route of infection of Tfh in macaques and humans appears to be via a CCR5-expressing pre-Tfh population. As the generation of Tfh are important for establishing effective immune responses during primary infections, Tfh are likely to be an early target of HIV-1 following transmission, creating an important component of the reservoir that has the potential to expand over time.</AbstractText>
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<Affiliation>School of Health and Biomedical Sciences, College of Science, Engineering and Health, RMIT University, Bundoora, VIC, Australia.</Affiliation>
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