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Host-Specific adaptation of HIV-1 Subtype B in the Japanese population

Chikata, T., Carlson, J.M., Tamura, Y., Borghan, M.A., Naruto, T., Hashimoto, M., Murakoshi, H., Le, A.Q., Mallal, S., John, M., Gatanaga, H., Oka, S., Brumme, Z.L. and Takiguchi, M. (2014) Host-Specific adaptation of HIV-1 Subtype B in the Japanese population. Journal of Virology, 88 (9). pp. 4764-4775.

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The extent to which HIV-1 clade B strains exhibit population-specific adaptations to host HLA alleles remains incompletely known, in part due to incomplete characterization of HLA-associated HIV-1 polymorphisms (HLA-APs) in different global populations. Moreover, it remains unknown to what extent the same HLA alleles may drive significantly different escape pathways across populations. As the Japanese population exhibits distinctive HLA class I allele distributions, comparative analysis of HLA-APs between HIV-1 clade B-infected Japanese and non-Asian cohorts could shed light on these questions. However HLA-APs remain incompletely mapped in Japan. In a cohort of 430 treatment-naïve Japanese with chronic HIV-1 clade B infection, we identified 284 HLA-APs in Gag, Pol and Nef using phylogenetically-corrected methods. The number of HLA-associated substitutions in Pol, notably those restricted by HLA-B*52:01, was weakly inversely correlated with plasma viral load (pVL), suggesting that the transmission and persistence of B*52:01-driven Pol mutations could modulate pVL. Differential selection of HLA-APs between HLA subtype members, including those differing only with respect to substitutions outside the peptide-binding groove, was observed, meriting further investigation as to their mechanisms of selection. Notably, two-thirds of HLA-AP identified in Japan had not been reported in previous studies of predominantly Caucasian cohorts, and were attributable to HLA alleles unique to, or enriched in, Japan. We also identified 71 cases where the same HLA allele drove significantly different escape pathways between Japan versus predominantly Caucasian cohorts. Our results underscore the distinct global evolution of HIV-1 clade B as a result of host population-specific cellular immune pressures.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: American Society for Microbiology
Copyright: © 2014 American Society for Microbiology
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