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adaptive evolution of hiv at hla epitopes is associated with ethnicity in canada自适应进化的艾滋病毒在加拿大的hla抗原表位与种族有关
Adaptive Evolution of HIV at HLA Epitopes Is Associated
with Ethnicity in Canada
1,2¤ ´ 2 1 1 1
Manon Ragonnet-Cronin , Stephane Aris-Brosou , Isabelle Joanisse , Harriet Merks , Dominic Vallee ,
1 1 1,3
Kyna Caminiti , Paul Sandstrom , James Brooks *
1 National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, Canada, 2 Department of Biology, University of Ottawa, Ottawa, Canada,
3 Department of Medicine, University of Ottawa, Ottawa, Canada
Abstract
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-naıve individuals in Canada. Phylogenetic analysis
showed no separation between pol sequences from five self-identified ethnic groups, yet fixation index (FST) values showed
significant divergence between ethnicities. A total of 17 amino acid sites showed an ethnic-specific fixation pattern
(0.015,FST ,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 61026 and p = 1.91 61027, respectively). Within the pol gene, eight site
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