Adaptive evolution of HIV at HLA epitopes is associated with ethnicity in Canada.
Host immune selection pressure influences the development of mutations that allow for HIV escape. Mutation patterns induced in HIV by the human leukocyte antigen (HLA) are HLA-allele specific. As ethnic groups have distinct and characteristic HLA allele frequencies, we can expect divergent viral evolution within ethnicities. Here, we have sequenced and analyzed the HIV pol gene from 1248 subtype B infected, treatment-naïve individuals in Canada. Phylogenetic analysis showed no separation between pol sequences from five self-identified ethnic groups, yet fixation index (F(ST)) values showed significant divergence between ethnicities. A total of 17 amino acid sites showed an ethnic-specific fixation pattern (0.015<F(ST) <0.060, p<0.01), and 27 codons were inferred to be under positive selection (p<0.01), with each set of sites strongly associated with HLA sites (p = 1.78×10(-6) and p = 1.91×10(-7), respectively). Within the pol gene, eight sites under HLA selective pressure were correlated with ethnicity, indicating 'adaptive divergence' between the groups studied. Our findings highlight challenges in HIV vaccine design in ethnically diverse countries with subtype B epidemics.
National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, Canada.
Manon
M
Ragonnet-Cronin
Stéphane
S
Aris-Brosou
Isabelle
I
Joanisse
Harriet
H
Merks
Dominic
D
Vallee
Kyna
K
Caminiti
Paul
P
Sandstrom
James
J
Brooks
D000222:Adaptation, Physiological / Q000235:genetics*; D000328:Adult; D000483:Alleles; D002170:Canada / Q000208:ethnology; D000939:Epitopes / Q000276:immunology*; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000208:ethnology* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012641:Selection, Genetic; D055815:Young Adult
D000939:Epitopes; D006680:HLA Antigens