Natural killer cells and human immunodeficiency virus

HIV-1 viraemia significantly impairs natural killer (NK) cell antiviral functions. Starting from acute infection, there is a pathologic redistribution of circulating NK cell subset that severely affects the ability of NK cells to eliminate HIV-1 infected cells. High frequencies of pathologic CD56neg/CD16pos NK cell subsets are associated with defective NK-DC interactions resulting in impaired activation and proliferation of NK cells, and deficient NK cell-mediated cytotoxicity and secretion of antiviral cytokines. Control of HIV-1 viraemia by antiretroviral therapy (ART) normalizes these parameters. TLR9 ligands may stimulate NK cells through pDC secretion of interferon (IFN)α. Cohorts of exposed, uninfected individuals and genetic studies show protective associations between some NK inhibitory receptors and their HLA class I molecule ligands. These data offer new molecular targets for HIV-1 control through restoration of NK cell functions. Natural killer (NK) cells are a subset of lymphoid cells that function as important mediators of innate immune defence against viruses and tumor cells. Understanding the biology of NK cells, particularly the identification of novel receptors and their ligands, has enhanced our knowledge on the potential role of NK cells in the immunopathogenesis of HIV infection. However, it is still unclear whether NK cells actually control HIV replication in vivo. Previous studies have attempted to evaluate the role of NK cells in the pathogenesis of several diseases or in the control of invading pathogens in nonhuman primates. The lack of specific markers that identify the entire simian NK cell population have significantly limited the understanding of the role of this population in disease states for which only nonhuman primates offer an appropriate animal model.