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

Borghan, M.A.

Brumme, Z.L.

Carlson, J.M.

Chikata, T.

Gatanaga, H.

Hashimoto, M.

John, M.

Mallal, S.

Naruto, T.

Oka, S.

Tamura, Y.

Yakiguchi, M.

Retrovirology

English

T Chikata

JM Carlson

Y Tamura

ZL Brumme

T Naruto

M Hashimoto

MA Borghan

M John

S Mallal

H Gatanaga

S Oka

M Takiguchi

Springer - Publisher Connector

POSTER PRESENTATION Open Access
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, M Takiguchi1
From AIDS Vaccine 2012
Boston, MA, USA. 9-12 September 2012
Background
It is assumed that the difference of HLA class I distribu-
tion 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 Japa-
nese and Caucasian infected with clade B virus is expected
to clarify the difference of HIV-1 evolution between both
populations.
Methods
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 regres-
sion model and false discovery rates to correct for multiple
tests.
Results
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 asso-
ciated with common HLA alleles, approximately 50%
were found in Caucasian population (IHAC cohort).
Conclusion
This study demonstrated that only 30% of HLA-APs
were shared between Caucasians and Japanese, indicat-
ing that the difference in HLA allele distributions
resulted in distinct HIV-1 evolution.
Author details
1Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
2eScience Group, Microsoft Research, Redmond, WA, USA. 3Faculty of Health
Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
4College of Arts and Sciences, University of Nizwa, Oman. 5Royal Perth
Hospital, Murdoch University, Perth, Australia. 6AIDS Clinical Center, National
Center for Global Health and Medicine, Tokyo, Japan.
Published: 13 September 2012
doi:10.1186/1742-4690-9-S2-P269
Cite this article as: Chikata et al.: HLA-associated viral polymorphism in
chronically HIV-1-infected Japanese cohort: analysis of four-digit HLA
allele level. Retrovirology 2012 9(Suppl 2):P269.
1Center for AIDS Research, Kumamoto University, Kumamoto, Japan
Full list of author information is available at the end of the article
Chikata et al. Retrovirology 2012, 9(Suppl 2):P269
http://www.retrovirology.com/content/9/S2/P269
© 2012 Chikata et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.


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

Background: 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. 



Methods: 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. 



Results: 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). 



Conclusion: 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

Takiguchi, M.

Research Repository

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

POSTER PRESENTATION Open AccessHLA-associated viral polymorphism in chronicallyHIV-1-infected Japanese cohort: analysis offour-digit HLA allele levelT Chikata1*, JM Carlson2, Y Tamura1, ZL Brumme3, T Naruto1, M Hashimoto1, MA Borghan4, M John5, S Mallal5,H Gatanaga6, S Oka6, M Takiguchi1From AIDS Vaccine 2012Boston, MA, USA. 9-12 September 2012BackgroundIt is assumed that the difference of HLA class I distribu-tion among ethnic populations influences HIV evolutionbecause HLA-restricted immune pressure selects escapemutations. Approximately 50% of HLA class I alleles areshared between Japanese and Caucasians. The analysis ofHLA-associated polymorphism (HLA-AP) in both Japa-nese and Caucasian infected with clade B virus is expectedto clarify the difference of HIV-1 evolution between bothpopulations.MethodsWe sequenced Gag, Pol, and Nef genes in 430 treatment-naïve Japanese chronically infected with HIV-1 clade Band then identified HLA-associated amino acids at eachcodon using a phylogenetically corrected logistic regres-sion model and false discovery rates to correct for multipletests.ResultsWe completely determined 400, 366, and 309 sequencesof Gag, Pol, and Nef, respectively, and then analyzedpolymorphisms associated with 78 four-digit HLA alleles(21 HLA-A, 38 HLA-B, and 19 HLA-C alleles). At thethreshold of q<0.2, we found 195 HLA-APs (67 in Gag,61 in Pol, and 67 in Nef). These polymorphisms wereobserved at 39 of 501 (7.8%) Gag, 42 of 1004 (4.2%) Pol,and 33 of 207 (16.0%) Nef codons. Ninety-six HLA-APsassociated with more than one HLA subtype allele weredetected in 4-digital HLA allele analysis. Approximately40% of HLA-APs were associated with HLA allelespredominantly found in Asia. Out of HLA-APs asso-ciated with common HLA alleles, approximately 50%were found in Caucasian population (IHAC cohort).ConclusionThis study demonstrated that only 30% of HLA-APswere shared between Caucasians and Japanese, indicat-ing that the difference in HLA allele distributionsresulted in distinct HIV-1 evolution.Author details1Center for AIDS Research, Kumamoto University, Kumamoto, Japan.2eScience Group, Microsoft Research, Redmond, WA, USA.3Faculty of HealthSciences, Simon Fraser University, Burnaby, British Columbia, Canada.4College of Arts and Sciences, University of Nizwa, Oman.5Royal PerthHospital, Murdoch University, Perth, Australia.6AIDS Clinical Center, NationalCenter for Global Health and Medicine, Tokyo, Japan.Published: 13 September 2012doi:10.1186/1742-4690-9-S2-P269Cite this article as: Chikata et al.: HLA-associated viral polymorphism inchronically HIV-1-infected Japanese cohort: analysis of four-digit HLAallele level. Retrovirology 2012 9(Suppl 2):P269.1Center for AIDS Research, Kumamoto University, Kumamoto, JapanFull list of author information is available at the end of the articleChikata et al. Retrovirology 2012, 9(Suppl 2):P269http://www.retrovirology.com/content/9/S2/P269© 2012 Chikata et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

http://researchrepository.murdoch.edu.au/10926/

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

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