Human immunodeficiency virus (HIV-1) infection selectively downregulates PD-1 expression in infected cells and protects the cells from early apoptosis in vitro and in vivo.
Programmed Death-1 (PD-1), a member of T cell costimulatory molecules is expressed in high levels on antigen specific T cells during chronic viral infection, whereas PD-1 expression in the context of HIV-1 infected CD4+ T cells is not known. Here we report that productively infected CD4+ T cells lose PD-1, whereas bystander cells were unaffected. Additionally, p24+/PD-1 negative cells are less susceptible to apoptosis compared to bystander cells in the same infected milieu. Similar results were observed in vivo, as infected T cells isolated from HIV-1+ individuals have significantly low level of PD-1 and the observed loss of PD-1 in vivo is independent of viral load, CD4 count, and/or antiviral treatment. Together these results indicate that productively infected cells are resistant to early apoptosis by downregulating PD-1, whereas PD-1 enhances the susceptibility of effector T cells to apoptosis suggesting a dual role for PD-1 during HIV-1 infection.
Venkatachari
Narasimhan J
NJ
Department of Infectious Diseases and Microbiology, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA 15261, USA.
Buchanan
William G
WG
Ayyavoo
Velpandi
V
D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015703:Antigens, CD; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000821:virology*; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D061026:Programmed Cell Death 1 Receptor; D019562:Viral Load
D044966:Anti-Retroviral Agents; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D016655:HIV Core Protein p24; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor