title: Pathologic natural killer cell subset redistribution in HIV-1 infection: new insights in pathophysiology and clinical outcomes.
abstract: Several lines of evidence indicate that the interaction of HIV-1 with NK cells markedly affects host immune responses and leads to a defective control of the virus. Until recently, it was generally believed that the absolute number of total circulating NK cells was decreased during the course of chronic and active phases of HIV-1 infection and that this explained, at least in part, the defective NK cell antiviral activities. However, scientific advances made over recent years have changed this concept and have clarified that HIV-1 viremia is associated with a pathologic redistribution rather than an absolute decrease in the number of circulating NK cells. In particular, the expansion of dysfunctional Siglec-7(neg) and/or CD56(neg) NK cell subsets expressing an aberrant repertoire of activating and inhibitory receptors has been associated with functional impairments of NK cells and with clinical outcomes of HIV-1 disease. Indeed, these pathologic NK cell populations often comprise the majority of NK cells in the presence of high levels of chronic HIV-1 viremia. The reasons for these NK cell aberrancies remain unknown, as freshly purified CD4(neg) NK cells are not productively infected by HIV-1. Disclosing the cellular and molecular mechanisms underlying such dysfunctions represents an important challenge of biomedical research, also considering that the presence of a rare KIR3DS1(pos) NK cell population represents a protective factor against HIV-1 disease progression. In this review, we will summarize the recent updates regarding NK cell pathophysiology during the course of HIV-1 infection.
authors.affiliation: Laboratory of Clinical and Experimental Immunology, IRCCS, Istituto Clinico Humanitas, Rozzano, Milano, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Brunetta
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Hudspeth
authors.forename: Domenico
authors.initials: D
authors.lastname: Mavilio
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D003586:Cytomegalovirus Infections / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D037102:Lectins / Q000032:analysis; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000032:analysis; D017452:Receptors, IgG / Q000032:analysis
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D019002:CD56 Antigen; D037102:Lectins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D017452:Receptors, IgG; C402206:SIGLEC7 protein, human