title: Release of Soluble Ligands for the Activating NKG2D Receptor: One More Immune Evasion Strategy Evolved by HIV-1 ?
abstract: Increasing lines of evidence indicate that NKG2D, an activating receptor of natural killer (NK) and CD8(+) T cells, plays an important role in immune responses against HIV-1. Through its ability to recognize a diverse array of ligands (NKG2DLs) induced by cell 'stress' such as viral infection, NKG2D delivers activating and co-stimulatory signals resulting in cytotoxicity and release of cytokines. Therefore, HIV-1 and other viruses have evolved clever mechanisms to counteract NKG2D-dependent immune responses. While, on one hand, the HIV-1 Vpr protein up-regulates NKG2DLs expression by activating the DNA damage response (DDR) pathway, other viral proteins (Nef and Vif) have developed the capacity to reduce NKG2DLs expression levels. In addition, recent evidences suggest that HIV-1-infected CD4(+) T cells may release NKG2DLs, particularly MICA, in soluble form, a phenomenon that has the potential to down-modulate NKG2D on circulating lymphocytes and allow evasion of NKG2D-mediated immune responses. Indeed, despite controversial, lower NKG2D expression was found on both NK and CD8(+) T cells in HIV-1-infected patients. This review discusses recent advances in the understanding of how HIV-1 affects the NKG2D/NKG2DLs system, with a special focus on virus-induced release of soluble NKG2DLs and its functional implications for the immune surveillance of the infected host.
authors.forename: Erica
authors.initials: E
authors.lastname: Giuliani
authors.forename: Lia
authors.initials: L
authors.lastname: Vassena
authors.forename: Cristina
authors.initials: C
authors.lastname: Cerboni
authors.affiliation: Laboratory of Immunoinfectivology, Children's Hospital Bambino Gesu, IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy. doria@uniroma2.it.
authors.forename: Margherita
authors.initials: M
authors.lastname: Doria
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D055808:Drug Discovery; D058851:GPI-Linked Proteins / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D057131:Immune Evasion / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D019899:Paracrine Communication / Q000187:drug effects / Q000502:physiology
chemical_list: D019380:Anti-HIV Agents; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; C423231:ULBP1 protein, human