Current HIV/AIDS Reports

, Volume 9, Issue 1, pp 81–90 | Cite as

Role of PD-1 in HIV Pathogenesis and as Target for Therapy

The Science of HIV (AL Landay, Section Editor)

Abstract

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.

Keywords

HIV 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 

Notes

Acknowledgments

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).

Disclosure

F. Porichis: none; D. E. Kaufmann: consultant to Bristol-Myers Squibb.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Division of Infectious Diseases, Massachusetts General HospitalBostonUSA
  3. 3.Massachusetts General Hospital East, Ragon Institute of MGH, MIT, and HarvardCharlestownUSA

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