title: Role of PD-1 in HIV pathogenesis and as target for therapy.
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.
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Filippos
authors.initials: F
authors.lastname: Porichis
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D051379:Mice; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000502:physiology*; D017735:Virus Latency / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor