Targeting HIV-1 Reservoirs in T Cell Subsets

Authors

Min Li
Marietta M Budai
Min Chen
Jin Wang

Publication Date

1-1-2023

Journal

Frontiers in Immunology

DOI

10.3389/fimmu.2023.1087923

PMID

36742330

PMCID

PMC9895780

PubMedCentral® Posted Date

1-20-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Mice, HIV Infections, HIV-1, Virus Replication, CD4-Positive T-Lymphocytes, Virus Latency, T-Lymphocyte Subsets, HIV Seropositivity, Proviruses, HIV-1, cell death, anti-apoptotic molecules, autophagy, latency reversal agents, T cell subsets, humanized mice

Abstract

The HIV-1 reservoirs harbor the latent proviruses that are integrated into the host genome. It is a challenging task to eradicate the proviruses in order to achieve an HIV cure. We have described a strategy for the clearance of HIV-1 infection through selective elimination of host cells harboring replication-competent HIV (SECH), by inhibition of autophagy and promotion of apoptosis during viral re-activation. HIV-1 can infect various CD4+ T cell subsets, but it is not known whether the SECH approach is equally effective in targeting HIV-1 reservoirs in these different subsets in vivo. In a humanized mouse model, we found that treatments of HIV-1 infection by suppressive antiretroviral therapy (ART) led to the establishment of latent HIV reservoirs in naïve, central memory and effector memory T cells. Moreover, SECH treatments could clear latent HIV-1 reservoirs in these different T cell subsets of humanized mice. Co-culture studies showed that T cell subsets latently infected by HIV-1, but not uninfected bystander cells, were susceptible to cell death induced by SECH treatments. Our study suggests that the SECH strategy is effective for specific targeting of latent HIV-1 reservoirs in different T cell subsets.