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- Paquin-Proulx, D, et al.
(author)
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Preferential and persistent impact of acute HIV-1 infection on CD4+ iNKT cells in colonic mucosa
- 2021
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 118:46
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Journal article (peer-reviewed)abstract
- Evidence suggests that HIV-1 disease progression is determined in the early stages of infection. Here, preinfection invariant natural killer T (iNKT) cell levels were predictive of the peak viral load during acute HIV-1 infection (AHI). Furthermore, iNKT cells were preferentially lost in AHI. This was particularly striking in the colonic mucosa, where iNKT cells were depleted more profoundly than conventional CD4+T cells. The initiation of antiretroviral therapy during AHI-prevented iNKT cell dysregulation in peripheral blood but not in the colonic mucosa. Overall, our results support a model in which iNKT cells are early and preferential targets for HIV-1 infection during AHI.
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- Dufour, C, et al.
(author)
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Phenotypic characterization of single CD4+ T cells harboring genetically intact and inducible HIV genomes
- 2023
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 1115-
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Journal article (peer-reviewed)abstract
- The phenotype of the rare HIV-infected cells persisting during antiretroviral therapies (ART) remains elusive. We developed a single-cell approach that combines the phenotypic analysis of HIV-infected cells with near full-length sequencing of their associated proviruses to characterize the viral reservoir in 6 male individuals on suppressive ART. We show that individual cells carrying clonally expanded identical proviruses display very diverse phenotypes, indicating that cellular proliferation contributes to the phenotypic diversification of the HIV reservoir. Unlike most viral genomes persisting on ART, inducible and translation-competent proviruses rarely present large deletions but are enriched in defects in the Ψ locus. Interestingly, the few cells harboring genetically intact and inducible viral genomes express higher levels of the integrin VLA-4 compared to uninfected cells or cells with defective proviruses. Viral outgrowth assay confirmed that memory CD4+ T cells expressing high levels of VLA-4 are highly enriched in replication-competent HIV (27-fold enrichment). We conclude that although clonal expansions diversify the phenotype of HIV reservoir cells, CD4+ T cells harboring replication-competent HIV retain VLA-4 expression.
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