PD-1 signaling in HIV and chronic viral infection--potential for therapeutic intervention?

Curr Med Chem. 2011;18(26):3971-80. doi: 10.2174/092986711796957239.


Programmed death-1 (PD-1) is a negative immunoregulatory cell surface receptor molecule whose interaction with its ligands PD-L1 and PD-L2 downmodulates T-cell immune responses. Originally investigated in the context of self-tolerance, PD-1 has more recently been discovered to be upregulated on T cells of HIV-infected individuals. High levels of PD-1 on HIV-infected T cells are correlated with viral load and with a state of cellular anergy, or ' exhaustion' that results in decreased cellular proliferation, cytotoxic function and cytokine secretion. The finding that interruption of PD-1 with its ligand PD-L1 rescues HIV-infected cells from this state of anergy or ' exhaustion' presents the promise for therapeutic intervention. Understanding the molecular signaling pathway(s) of PD-1 may provide opportunities for therapeutic intervention, that may serve as adjunctive therapies to HIV vaccine development. Evidence to date suggests that PD-1 exerts its regulatory effect by interfering with T cell receptor signaling. While certain molecular signals in the PD-1 pathway have been identified, their precise roles and mechanisms of action remain poorly understood. This article reviews what is currently known about PD-1 signaling in human T cells, and more specifically in T cells of individuals chronically infected with certain viruses such as HIV.

Publication types

  • Review

MeSH terms

  • Chronic Disease / prevention & control
  • Chronic Disease / therapy
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • HIV Infections / prevention & control*
  • HIV Infections / therapy
  • HIV-1 / immunology*
  • Humans
  • Programmed Cell Death 1 Receptor / immunology*
  • Programmed Cell Death 1 Receptor / metabolism
  • Programmed Cell Death 1 Receptor / therapeutic use


  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor