Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection

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Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection


نویسنده	adland e. ,paioni p. ,thobakgale c. ,laker l. ,mori l. ,muenchhoff m. ,csala a. ,clapson m. ,flynn j. ,novelli v. ,hurst j. ,naidoo v. ,shapiro r. ,huang k.-h.g. ,frater j. ,prendergast a. ,prado j.g. ,ndung’u t. ,walker b.d. ,carrington m. ,jooste p. ,goulder p.j.r.
منبع	plos pathogens - 2015 - دوره : 11 - شماره : 6
چکیده	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-b57,hla-b58:01 and hla-b81:01,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-b18:01/45:01/58:02 (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. © 2015 adland et al.

آدرس	department of paediatrics,university of oxford,peter medawar building for pathogen research,oxford, United Kingdom, department of paediatrics,university of oxford,peter medawar building for pathogen research,oxford, United Kingdom, hiv pathogenesis programme,doris duke medical research institute,university of kwazulu-natal,durban, South Africa, paediatric department,kimberley hospital,northern cape, South Africa, paediatric department,kimberley hospital,northern cape, South Africa, department of paediatrics,university of oxford,peter medawar building for pathogen research,oxford,united kingdom,hiv pathogenesis programme,doris duke medical research institute,university of kwazulu-natal,durban, South Africa, department of paediatrics,university of oxford,peter medawar building for pathogen research,oxford, United Kingdom, department of paediatric infectious diseases,great ormond st hospital for children,london, United Kingdom, department of paediatric infectious diseases,great ormond st hospital for children,london, United Kingdom, department of paediatric infectious diseases,great ormond st hospital for children,london, United Kingdom, the institute for emerging infections,the oxford martin school,university of oxford,oxford,united kingdom,nuffield department of medicine,university of oxford,peter medawar building for pathogen research,oxford,united kingdom,oxford national institute of health research,biomedical research centre,oxford, United Kingdom, hiv pathogenesis programme,doris duke medical research institute,university of kwazulu-natal,durban, South Africa, botswana harvard aids institute partnership,gaborone, Botswana, the institute for emerging infections,the oxford martin school,university of oxford,oxford,united kingdom,nuffield department of medicine,university of oxford,peter medawar building for pathogen research,oxford, United Kingdom, the institute for emerging infections,the oxford martin school,university of oxford,oxford,united kingdom,nuffield department of medicine,university of oxford,peter medawar building for pathogen research,oxford,united kingdom,oxford national institute of health research,biomedical research centre,oxford, United Kingdom, centre for paediatrics,blizard institute,queen mary university of london,london,united kingdom,zvitambo institute for maternal and child health research,harare, Zimbabwe, aids research institute irsicaixa,institut d’investigació en ciències de la salut germans trias i pujol,badalona,barcelona, Spain, hiv pathogenesis programme,doris duke medical research institute,university of kwazulu-natal,durban,south africa,the ragon institute of massachusetts general hospital (mgh),massachusetts institute of technology (mit),and harvard university,boston,ma,united states,kwazulu-natal research institute for tuberculosis and hiv,university of kwazulu-natal,durban,south africa,max planck institute for infection biology,berlin, Germany, hiv pathogenesis programme,doris duke medical research institute,university of kwazulu-natal,durban,south africa,the ragon institute of massachusetts general hospital (mgh),massachusetts institute of technology (mit),and harvard university,boston,ma, United States, the ragon institute of massachusetts general hospital (mgh),massachusetts institute of technology (mit),and harvard university,boston,ma,united states,center for cancer research,national cancer institute,frederick,md, United States, paediatric department,kimberley hospital,northern cape, South Africa, department of paediatrics,university of oxford,peter medawar building for pathogen research,oxford,united kingdom,hiv pathogenesis programme,doris duke medical research institute,university of kwazulu-natal,durban,south africa,department of paediatric infectious diseases,great ormond st hospital for children,london, United Kingdom



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