title: A whole-genome association study of major determinants for host control of HIV-1.
abstract: Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy, we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele human leukocyte antigen (HLA)-B*5701, whereas a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated two genes, one of which encodes an RNA polymerase I subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.
authors.affiliation: Center for Population Genomics and Pharmacogenetics, Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27710, USA.
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Shianna
authors.forename: Dongliang
authors.initials: D
authors.lastname: Ge
authors.forename: Sara
authors.initials: S
authors.lastname: Colombo
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Mike
authors.initials: M
authors.lastname: Weale
authors.forename: Kunlin
authors.initials: K
authors.lastname: Zhang
authors.forename: Curtis
authors.initials: C
authors.lastname: Gumbs
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
authors.forename: Patrick
authors.initials: P
authors.lastname: Francioli
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
authors.forename: José M
authors.initials: JM
authors.lastname: Miro
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.forename: Jason P
authors.initials: JP
authors.lastname: Smith
authors.forename: Josiane
authors.initials: J
authors.lastname: Wyniger
authors.forename: Patrick
authors.initials: P
authors.lastname: Descombes
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
mesh_terms: D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005805:Genes, MHC Class I; D015894:Genome, Human; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000628:therapy / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D015235:HLA-B Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012044:Regression Analysis; D019562:Viral Load
chemical_list: D004268:DNA-Binding Proteins; C080521:HCP5 long noncoding RNA, human; D015235:HLA-B Antigens; C484830:HLA-B*57:01 antigen; D015236:HLA-C Antigens; D017874:Immediate-Early Proteins; C406241:POLR1H protein, human; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C444639:RNF39 protein, human