A whole-genome association study of major determinants for host control of HIV-1.
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.
Fellay
Jacques
J
Center for Population Genomics and Pharmacogenetics, Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27710, USA.
Shianna
Kevin V
KV
Ge
Dongliang
D
Colombo
Sara
S
Ledergerber
Bruno
B
Weale
Mike
M
Zhang
Kunlin
K
Gumbs
Curtis
C
Castagna
Antonella
A
Cossarizza
Andrea
A
Cozzi-Lepri
Alessandro
A
De Luca
Andrea
A
Easterbrook
Philippa
P
Francioli
Patrick
P
Mallal
Simon
S
Martinez-Picado
Javier
J
Miro
José M
JM
Obel
Niels
N
Smith
Jason P
JP
Wyniger
Josiane
J
Descombes
Patrick
P
Antonarakis
Stylianos E
SE
Letvin
Norman L
NL
McMichael
Andrew J
AJ
Haynes
Barton F
BF
Telenti
Amalio
A
Goldstein
David B
DB
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
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