HIV-1 immunopathogenesis: how good interferon turns bad.
The hallmark of acquired immunodeficiency syndrome (AIDS) is the progressive loss of CD4+ T cells that results from infection with human immunodeficiency virus type-1 (HIV-1). Despite 25 years of AIDS research, questions remain concerning the mechanisms responsible for HIV-induced CD4+ T cell depletion. Here we briefly review the in vitro and in vivo literature concerning the protective role of interferon-alpha (IFN-alpha) in HIV/AIDS. We then develop a laboratory- and clinically supported model of CD4+ T cell apoptosis in which either infectious or noninfectious HIV-1 induces the production of type I interferon by plasmacytoid dendritic cells (pDC). The interferon produced binds to its receptor on primary CD4+ T cells resulting in membrane expression of the TNF-related apoptosis-inducing ligand (TRAIL) death molecule. The binding of infectious or noninfectious HIV-1 to CD4 on these T cells results in expression of the TRAIL death receptor 5 (DR5), leading to the selective death of HIV-exposed CD4+ T cells.
Herbeuval
Jean-Philippe
JP
UMR CNRS 8147, Hôpital Necker, Université Paris V, Paris, France.
Shearer
Gene M
GM
D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015658:HIV Infections / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D008954:Models, Biological; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
D016898:Interferon-alpha; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human