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This article is part of the supplement: AIDS Vaccine 2012

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HLA-associated viral polymorphism in chronically HIV-1-infected Japanese cohort: analysis of four-digit HLA allele level

T Chikata1*, JM Carlson2, Y Tamura1, ZL Brumme3, T Naruto1, M Hashimoto1, MA Borghan4, M John5, S Mallal5, H Gatanaga6, S Oka6 and M Takiguchi1

  • * Corresponding author: T Chikata

Author Affiliations

1 Center for AIDS Research, Kumamoto University, Kumamoto, Japan

2 eScience Group, Microsoft Research, Redmond, WA, USA

3 Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada

4 College of Arts and Sciences, University of Nizwa, Oman

5 Royal Perth Hospital, Murdoch University, Perth, Australia

6 AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan

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Retrovirology 2012, 9(Suppl 2):P269  doi:10.1186/1742-4690-9-S2-P269

The electronic version of this article is the complete one and can be found online at:

Published:13 September 2012

© 2012 Chikata et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


It is assumed that the difference of HLA class I distribution among ethnic populations influences HIV evolution because HLA-restricted immune pressure selects escape mutations. Approximately 50% of HLA class I alleles are shared between Japanese and Caucasians. The analysis of HLA-associated polymorphism (HLA-AP) in both Japanese and Caucasian infected with clade B virus is expected to clarify the difference of HIV-1 evolution between both populations.


We sequenced Gag, Pol, and Nef genes in 430 treatment-naïve Japanese chronically infected with HIV-1 clade B and then identified HLA-associated amino acids at each codon using a phylogenetically corrected logistic regression model and false discovery rates to correct for multiple tests.


We completely determined 400, 366, and 309 sequences of Gag, Pol, and Nef, respectively, and then analyzed polymorphisms associated with 78 four-digit HLA alleles (21 HLA-A, 38 HLA-B, and 19 HLA-C alleles). At the threshold of q<0.2, we found 195 HLA-APs (67 in Gag, 61 in Pol, and 67 in Nef). These polymorphisms were observed at 39 of 501 (7.8%) Gag, 42 of 1004 (4.2%) Pol, and 33 of 207 (16.0%) Nef codons. Ninety-six HLA-APs associated with more than one HLA subtype allele were detected in 4-digital HLA allele analysis. Approximately 40% of HLA-APs were associated with HLA alleles predominantly found in Asia. Out of HLA-APs associated with common HLA alleles, approximately 50% were found in Caucasian population (IHAC cohort).


This study demonstrated that only 30% of HLA-APs were shared between Caucasians and Japanese, indicating that the difference in HLA allele distributions resulted in distinct HIV-1 evolution.