Expression Profile and Biological Role of Immune Checkpoints in Disease Progression of HIV/SIV Infection

During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), lymphocyte-activation gene-3 (LAG-3), T cell immunoglobulin and mucin domain-3 (Tim-3), CD160, 2B4 (CD244), and V-domain Ig suppressor of T cell activation (VISTA), can lead to chronic T cell exhaustion. These ICs play predominant roles in regulating the progression of HIV/SIV infection by mediating T cell responses as well as enriching latent viral reservoirs. It has been demonstrated that enhanced expression of ICs on CD4(+) and CD8(+) T cells could inhibit cell proliferation and cytokine production. Overexpression of ICs on CD4(+) T cells could also format and prolong HIV/SIV persistence. IC blockers have shown promising clinical results in HIV therapy, implying that targeting ICs may optimize antiretroviral therapy in the context of HIV suppression. Here, we systematically review the expression profile, biological regulation, and therapeutic efficacy of targeted immune checkpoints in HIV/SIV infection.

Automated summary

During HIV/SIV infection, upregulated immune checkpoint markers can lead to chronic T cell exhaustion and regulate disease progression by mediating T cell responses and enriching viral reservoirs. Overexpression of these markers inhibits cell proliferation and cytokine production, affecting viral persistence. Targeting immune checkpoints has shown potential therapeutic efficacy in HIV treatment.