title: 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.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Sakamoto, Nagasaki City, Nagasaki, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mori
authors.forename: Nuanjun
authors.initials: N
authors.lastname: Wichukchinda
authors.forename: Reiko
authors.initials: R
authors.lastname: Miyahara
authors.forename: Archawin
authors.initials: A
authors.lastname: Rojanawiwat
authors.forename: Panita
authors.initials: P
authors.lastname: Pathipvanich
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Maekawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Philip
authors.initials: P
authors.lastname: Goulder
authors.forename: Michio
authors.initials: M
authors.lastname: Yasunami
authors.forename: Koya
authors.initials: K
authors.lastname: Ariyoshi
authors.forename: Pathom
authors.initials: P
authors.lastname: Sawanpanyalert
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D044466:Asian People; D003430:Cross-Sectional Studies; D060467:Disease Resistance; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D015797:HLA-B35 Antigen / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013785:Thailand; D019562:Viral Load; D055815:Young Adult
chemical_list: D015797:HLA-B35 Antigen