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EnglishHIV-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), 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 | |
| Autori: | BRUNETTA, ENRICO (Primo) MAVILIO, DOMENICO (Corresponding) | |
| Parole Chiave: | NK cells; activating receptors; dendritic cells; infection; sialoadhesin; responses; immunodeficiency; identification; recognition; specifity | |
| 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: | 2009 | |
| Rivista: | ||
| Tipologia: | Article (author) | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1182/blood-2009-06-226332 | |
| Appare nelle tipologie: | 01 - Articolo su periodico |
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| T:Brunetta et al. Blood 2009.pdf | Publisher's version/PDF | Administrator Richiedi una copia |
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