title: Clade-specific evolution mediated by HLA-B*57/5801 in human immunodeficiency virus type 1 clade A1 p24.
abstract: HLA-B*57-mediated selection pressure leads to a typical escape pathway in human immunodeficiency virus type 1 (HIV-1) CD8 epitopes such as TW10. Whether this T242N pathway is shared by all clades remains unknown. We therefore assessed the nature of HLA-B*57 selection in a large, observational Kenyan cohort where clades A1 and D predominate. While T242N was ubiquitous in clade D HLA-B*57(+) subjects, this mutation was rare (15%) in clade A1. Instead, P243T and I247L were selected by clade A1-infected HLA-B*57 subjects but not by HLA-B*5801(+) subjects. Our data suggest that clade A1 consensus proline at Gag residue 243 might represent an inherent block to T242N escape in clade A1. We confirmed immunologically that P243T and I247L likely represent escape mutations. HLA-B*57 evolution also differed between clades in the KF11 and IW9 epitopes. A better understanding of clade-specific evolution is important for the development of HIV vaccines in regions with multiple clades.
authors.affiliation: Departments of Medical Microbiology1 and Immunolgy,5 University of Manitoba, Winnipeg, Canada. sijuisijali@gmail.com
authors.forename: Lyle R
authors.initials: LR
authors.lastname: McKinnon
authors.forename: Rupert
authors.initials: R
authors.lastname: Capina
authors.forename: Harold
authors.initials: H
authors.lastname: Peters
authors.forename: Mark
authors.initials: M
authors.lastname: Mendoza
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.forename: Charles
authors.initials: C
authors.lastname: Wachihi
authors.forename: Anthony
authors.initials: A
authors.lastname: Kariri
authors.forename: Makobu
authors.initials: M
authors.lastname: Kimani
authors.forename: Meika
authors.initials: M
authors.lastname: Richmond
authors.forename: Sandy Koesters
authors.initials: SK
authors.lastname: Kiazyk
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fowke
authors.forename: Walter
authors.initials: W
authors.lastname: Jaoko
authors.forename: Ma
authors.initials: M
authors.lastname: Luo
authors.forename: T Blake
authors.initials: TB
authors.lastname: Ball
authors.forename: Francis A
authors.initials: FA
authors.lastname: Plummer
mesh_terms: D000220:Adaptation, Biological; D019943:Amino Acid Substitution / Q000235:genetics; D015331:Cohort Studies; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D019143:Evolution, Molecular; D016655:HIV Core Protein p24 / Q000235:genetics* / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D007630:Kenya; D020125:Mutation, Missense; D012641:Selection, Genetic
chemical_list: D018984:Epitopes, T-Lymphocyte; D016655:HIV Core Protein p24; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; C514799:p24 protein, Human Immunodeficiency Virus Type 1