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AIDS:
doi: 10.1097/QAD.0000000000000206
Basic Science

HLA-B∗35:05 is a protective allele with a unique structure among HIV-1 CRF01_AE-infected Thais, in whom the B∗57 frequency is low

Mori, Masahiko; Wichukchinda, Nuanjun; Miyahara, Reiko; Rojanawiwat, Archawin; Pathipvanich, Panita; Maekawa, Tomoyuki; Miura, Toshiyuki; Goulder, Philip; Yasunami, Michio; Ariyoshi, Koya; Sawanpanyalert, Pathom

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Abstract

Objective:

To identify protective human leukocyte antigen (HLA) alleles in an HIV-infected south-east Asian population, in whom HLA-B∗57 prevalence is lower than other ethnic groups, and HIV-1 CRF01_AE is the dominant circulating subtype.

Design:

Cross-sectional study of Thai patients with chronic HIV infection.

Methods:

Five hundred and fifty-seven HIV-1 CRF01_AE-infected Thais were recruited. Their HLA type and viral load were determined to statistically analyze the association of each allele in viral control. In-silico molecular dynamics was also used to evaluate the effect of HLA structure variants on epitope binding.

Results:

HLA-B∗35:05 was identified as the most protective allele (P = 0.003, q = 0.17), along with HLA-B∗57:01 (P = 0.044, q = 0.31). Structurally, HLA-B∗35:05 belonged to the HLA-B∗35-PY group of HLA-B∗35 alleles; however, unlike the other HLA-B∗35 alleles that carry Arg (R) at residue 97, it has unique sequences at T94, L95, and S97, located within the peptide-binding groove. Analysis of the three-dimensional HLA structure and molecular dynamics indicates that S97 in HLA-B∗35:05 leads to less flexibility in the groove, and shorter distances between the α-helixes compared with the disease-susceptible HLA-B∗35-PY allele, HLA-B∗35:01.

Conclusion:

These data indicate the existence of a protective effect of HLA-B∗57 across ethnic groups and highlight HLA-B∗35:05 as an allele uniquely protective in subtype CRF01_AE-infected Thais. The divergence of HLA-B∗35:05 from conventional HLA-B∗35-PY structural sequences at the peptide-binding groove is consistent with previous studies that have identified HLA residue 97 as strongly influential in shaping HLA impact on immune control of HIV, and that a more restricted peptide-binding motif may be associated with improved control.

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

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