Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection
Adland, Emily (University of Oxford)
Paioni, Paolo (University of Oxford)
Thobakgale, Christina (University of KwaZulu-Natal (Durban, Sud-àfrica))
Laker, Leana (Kimberley Hospital (Northern Cape, Sud-àfrica))
Mori, Luisa (Kimberley Hospital (Northern Cape, Sud-àfrica))
Muenchhoff, Maximilian (University of Oxford)
Csala, Anna (University of Oxford)
Clapson, Margaret (Saint Hospital for Children (London, Gran Bretanya))
Flynn, Jacquie (Saint Hospital for Children (London, Gran Bretanya))
Novelli, Vas (Saint Hospital for Children (London, Gran Bretanya))
Hurst, Jacob (University of Oxford)
Naidoo, Vanessa (University of KwaZulu-Natal (Durban, Sud-àfrica))
Shapiro, Roger (Botswana Harvard AIDS Institute Partnership (Gaborone, Botswana))
Gary, Kuan-Hsiang Huang (University of Oxford)
Frater, John (University of Oxford)
Prendergast, Andrew (Queen Mary University of London)
Prado, Julia G.. (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Ndung'u, Thumbi (University of KwaZulu-Natal (Durban, Sud-àfrica))
Walker, Bruce D. (University of Oxford)
Carrington, Mary (National Cancer Institute (Maryland, Estats Units d'Amèrica))
Jooste, Pieter (Kimberley Hospital (Northern Cape, Sud-àfrica))
Goulder, Philip J. R. (University of Oxford)

Data:	2015
Resum:	Abstract. HLA class I polymorphism has a major influence on adult HIV disease progression. An important mechanism mediating this effect is the impact on viral replicative capacity (VRC) of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses. Factors that contribute to slow progression in pediatric HIV infection are less well understood. We here investigate the relationship between VRC and disease progression in pediatric infection, and the effect of HLA on VRC and on disease outcome in adult and pediatric infection. Studying a South African cohort of >350 ART-naïve, HIV-infected children and their mothers, we first observed that pediatric disease progression is significantly correlated with VRC. As expected, VRCs in mother-child pairs were strongly correlated (p = 0. 004). The impact of the protective HLA alleles, HLA-B*57, HLA-B*58:01 and HLA-B*81:01, resulted in significantly lower VRCs in adults (p<0. 0001), but not in children. Similarly, in adults, but not in children, VRCs were significantly higher in subjects expressing the disease-susceptible alleles HLA-B*18:01/45:01/58:02 (p = 0. 007). Irrespective of the subject, VRCs were strongly correlated with the number of Gag CD8+ T-cell escape mutants driven by HLA-B*57/58:01/81:01 present in each virus (p = 0. 0002). In contrast to the impact of VRC common to progression in adults and children, the HLA effects on disease outcome, that are substantial in adults, are small and statistically insignificant in infected children. These data further highlight the important role that VRC plays both in adult and pediatric progression, and demonstrate that HLA-independent factors, yet to be fully defined, are predominantly responsible for pediatric non-progression.
Nota:	Ajuts: Wellcome Trust (WT104748MA, PJRG), South African DST/NRF Research Chairs Initiative, Victor Daitz Foundation, International Early Career Scientist Award i Miguel Servet Contract (MS09/00279)
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PLOS pathogens, Vol. 11 Núm. 6 (June 2015) , ISSN 1553-7374

DOI: 10.1371/journal.ppat.1004954
PMID: 26076345

26 p, 2.7 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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