title: The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer-cell subsets associated with high levels of HIV-1 viremia.
abstract: HIV-1 has developed several strategies to evade natural killer (NK)-cell antiviral functions. One of these mechanisms is the HIV-1-induced expansion of highly dysfunctional NK-cell subsets. Here, we analyze a large cohort of HIV-1-infected patients in early or chronic phases of infection, both cross-sectionally and longitudinally. We demonstrate that a striking decrease in the surface expression of sialic acid-binding immunoglobulin-like lectin 7 (Siglec-7) represents the earliest marker of the aberrant NK-cell dysregulation, which precedes the down-modulation of CD56 mostly occurring in patients with chronic HIV-1 viremia. The combined detection of Siglec-7 and CD56 allows the identification of 2 new pathologic NK-cell subsets expanded preferentially in early (Siglec-7-/CD56+) or chronic (Siglec-7-/CD56-) stages of HIV-1 infection. Remarkably, these phenotypic abnormalities were directly associated with progressive and distinct impairments of NK-cell functions. The aforementioned NK-cell aberrancies could be observed only in the presence of high levels of viral replication and not in patients with low or undetectable HIV-1 viremia, such as long-term nonprogressors or patients having undergone antiretroviral therapy. High frequencies of Siglec-7-/CD56+ and Siglec-7-/CD56- pathologic NK cells reflect the immune and clinical status of HIV-1 infection and can also track the effectiveness of therapy.
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Clinico Humanitas, Rozzano, Milano, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Brunetta
authors.forename: Manuela
authors.initials: M
authors.lastname: Fogli
authors.forename: Stefania
authors.initials: S
authors.lastname: Varchetta
authors.forename: Luisa
authors.initials: L
authors.lastname: Bozzo
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Hudspeth
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcenaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Domenico
authors.initials: D
authors.lastname: Mavilio
mesh_terms: D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D019002:CD56 Antigen / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D037102:Lectins / Q000276:immunology*; D008297:Male; D014766:Viremia / Q000276:immunology* / Q000473:pathology; D014779:Virus Replication / Q000276:immunology*
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D019002:CD56 Antigen; D037102:Lectins; C402206:SIGLEC7 protein, human