title: Innate immunity and HIV-1 infection.
abstract: HIV-1 is predominantly transmitted through mucosal tissues, targeting CD4(+)CCR5(+) T cells, 50% of which are destroyed within 2 weeks of infection. Conventional vaccination strategies have so far failed to prevent HIV-1 infection. Neither antibodies nor cytotoxic lymphocytes are capable of mounting a sufficiently rapid immune response to prevent early destruction of these cells. However, innate immunity is an early-response system, largely independent of prior encounter with a pathogen. Innate immunity can be classified into cellular, extracellular, and intracellular components, each of which is exemplified in this review by γδ T cells, CC chemokines, and APOBEC3G, respectively. First, γδ T cells are found predominantly in mucosal tissues and produce cytokines, CC chemokines, and antiviral factors. Second, the CC chemokines CCL-3, CCL-4, and CCL-5 can be upregulated by immunization of macaques with SIVgp120 and gag p27, and these can bind and downmodulate CCR5, thereby inhibiting HIV-1 entry into the host cells. Third, APOBEC3G is generated and maintained following rectal mucosal immunization in rhesus macaques for over 17 weeks, and the innate anti-SIV factor is generated by CD4(+)CD95(+)CCR7(-) effector memory T cells. Thus, innate anti-HIV-1 or SIV immunity can be linked with immune memory, mediated by CD4(+) T cells generating APOBEC3G. The multiple innate functions may mount an early anti-HIV-1 response and either prevent viral transmission or contain the virus until an effective adaptive immune response develops.
authors: Mucosal Immunology Unit, Kings College London at Guy's Hospital, London, UK. Thomas.lehner@kcl.ac.uk
authors: T
authors: T
authors: Lehner
authors: Y
authors: Y
authors: Wang
authors: T
authors: T
authors: Whittall
authors: T
authors: T
authors: Seidl
mesh_terms: D000071480:APOBEC-3G Deaminase; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019742:Chemokines, CC / Q000276:immunology; D003564:Cytidine Deaminase / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000276:immunology; D007801:Langerhans Cells / Q000502:physiology; D008253:Macaca mulatta / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D019713:Receptors, CCR5 / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014779:Virus Replication
chemical_list: D019742:Chemokines, CC; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019713:Receptors, CCR5; D007372:Interferons; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase