Role of PD-1 in HIV Pathogenesis and as Target for Therapy
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Major advances in Antiretroviral Therapy (ART) have resulted in a dramatic decline in HIV-related deaths. However, no current treatment regimen leads to viral eradication or restoration of HIV-specific immune responses capable of durable viral control after cessation of ART. Thus, there is a need for novel interventions that could complement ART in order to eliminate virus or reach a state of “functional cure.” It has been shown in murine models and humans that the negative co-signaling molecule programmed-death 1 (PD-1) plays an active and reversible role in mediating T-cell exhaustion in chronic infections. This review summarizes recent advances in our understanding of the PD-1 pathway in HIV infection, and the lessons learned from studies in the SIV model and cancer. We discuss the potential of immunotherapeutic interventions targeting PD-1 in order to augment immune responses or facilitate viral eradication. We also present the challenges to therapies targeting immunoregulatory networks.
KeywordsHIV AIDS Chronic viral infection T-cell exhaustion Programmed-death 1 (PD-1) Programmed death-ligand 1 (PD-L1) Programmed death-ligand 2 (PD-L2) CD4 T cell CD8 T cell Monocytes B cell Viral reservoirs Viral eradication Elite controllers Immunotherapy Mucosal immunity
D.E.K. is supported by grants from the National Institutes of Health (NIH RO1 HL 092565 and P01AI-080192). F.P. is supported by a fellowship grant from Executive Committee on Research of the Massachusetts General Hospital (ECOR).
F. Porichis: none; D. E. Kaufmann: consultant to Bristol-Myers Squibb.
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