HIV evolution: CTL escape mutation and reversion after transmission.

Leslie, A J; Pfafferott, K J; Chetty, P; Draenert, R; Addo, M M; Feeney, M; Tang, Y; Holmes, E C; Allen, T; Prado, J G; Altfeld, M; Brander, C; Dixon, C; Ramduth, D; Jeena, P; Thomas, S A; St John, A; Roach, T A; Kupfer, B; Luzzi, G; Edwards, A; Taylor, G; Lyall, H; Tudor-Williams, G; Novelli, V; Martinez-Picado, J; Kiepiela, P; Walker, B D; Goulder, P J R

Leslie, A J; Pfafferott, K J; Chetty, P; Draenert, R; Addo, M M; Feeney, M; Tang, Y; Holmes, E C; Allen, T; Prado, J G; Altfeld, M; Brander, C; Dixon, C; Ramduth, D; Jeena, P; Thomas, S A; St John, A; Roach, T A; Kupfer, B; Luzzi, G; Edwards, A; Taylor, G; Lyall, H; Tudor-Williams, G; Novelli, V; Martinez-Picado, J; Kiepiela, P; Walker, B D; Goulder, P J R.

Afiliación

Leslie AJ; Department of Pediatrics, Fuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.

Nat Med ; 10(3): 282-9, 2004 Mar.

Article en En | MEDLINE | ID: mdl-14770175

RESUMEN

Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 patients drawn from the B- and C-clade epidemics, focusing on human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801, which are associated with long-term HIV control and are therefore likely to exert strong selection pressure on the virus. The CTL response dominating acute infection in HLA-B57/5801-positive subjects drove positive selection of an escape mutation that reverted to wild-type after transmission to HLA-B57/5801-negative individuals. A second escape mutation within the epitope, by contrast, was maintained after transmission. These data show that the process of accumulation of escape mutations within HIV is not inevitable. Complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level.

Asunto(s)

Evolución Molecular; Infecciones por VIH/virología; VIH-1/fisiología; Mutación; Linfocitos T Citotóxicos/inmunología; Adulto; Secuencia de Aminoácidos; Niño; Epítopos; Femenino; Variación Genética; Infecciones por VIH/inmunología; Infecciones por VIH/transmisión; VIH-1/genética; VIH-1/inmunología; Antígenos HLA-B/genética; Antígenos HLA-B/inmunología; Humanos; Transmisión Vertical de Enfermedad Infecciosa; Funciones de Verosimilitud; Filogenia; Selección Genética; Linfocitos T Citotóxicos/metabolismo; Carga Viral

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Citotóxicos / Infecciones por VIH / VIH-1 / Evolución Molecular / Mutación Límite: Adult / Child / Female / Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2004 Tipo del documento: Article Pais de publicación: Estados Unidos

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