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.
The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer-cell subsets associated with high levels of HIV-1 viremia / E. Brunetta, M. Fogli, S. Varchetta, L. Bozzo, K.L. Hudspeth, E. Marcenaro, A. Moretta, D. Mavilio. - In: BLOOD. - ISSN 0006-4971. - 114:18(2009 Oct 29), pp. 3822-3830.
|Titolo:||The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer-cell subsets associated with high levels of HIV-1 viremia|
BRUNETTA, ENRICO (Primo)
MAVILIO, DOMENICO (Ultimo)
|Parole Chiave:||Antigens, CD56 ; Antigens, Differentiation, Myelomonocytic ; Cohort Studies ; Female ; HIV Infections ; HIV-1 ; Humans ; Killer Cells, Natural ; Lectins ; Male ; Viremia ; Virus Replication|
|Settore Scientifico Disciplinare:||Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio|
Settore MED/04 - Patologia Generale
Settore MED/17 - Malattie Infettive
|Data di pubblicazione:||29-ott-2009|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1182/blood-2009-06-226332|
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