Journal
FRONTIERS IN IMMUNOLOGY
Volume 14, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2023.1087923
Keywords
HIV-1; cell death; anti-apoptotic molecules; autophagy; latency reversal agents; T cell subsets; humanized mice
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The study presents a strategy called selective elimination of host cells harboring replication-competent HIV (SECH) that targets HIV-1 reservoirs through inhibition of autophagy and promotion of apoptosis. This strategy has been shown to effectively clear latent HIV-1 reservoirs in different subsets of T cells. The findings provide a potential method for eradicating HIV-1 infection.
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 naive, 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.
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