title: Adaptation of HIV-1 to human leukocyte antigen class I.
abstract: The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host-pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8(+) T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection. Mutation within these epitopes can allow viral escape from CD8(+) T-cell recognition. Here we analysed viral sequences and HLA alleles from >2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128-135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8(+) T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P < 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.
authors.affiliation: Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Katja
authors.initials: K
authors.lastname: Pfafferott
authors.forename: John
authors.initials: J
authors.lastname: Frater
authors.forename: Philippa
authors.initials: P
authors.lastname: Matthews
authors.forename: Rebecca
authors.initials: R
authors.lastname: Payne
authors.forename: Marylyn
authors.initials: M
authors.lastname: Addo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.forename: Mamoru
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hachiya
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Koizumi
authors.forename: Nozomi
authors.initials: N
authors.lastname: Kuse
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.forename: Anna
authors.initials: A
authors.lastname: Duda
authors.forename: Andrew
authors.initials: A
authors.lastname: Prendergast
authors.forename: Hayley
authors.initials: H
authors.lastname: Crawford
authors.forename: Alasdair
authors.initials: A
authors.lastname: Leslie
authors.forename: Zabrina
authors.initials: Z
authors.lastname: Brumme
authors.forename: Chanson
authors.initials: C
authors.lastname: Brumme
authors.forename: Todd
authors.initials: T
authors.lastname: Allen
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Richard
authors.initials: R
authors.lastname: Kaslow
authors.forename: James
authors.initials: J
authors.lastname: Tang
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.forename: Joseph
authors.initials: J
authors.lastname: Mulenga
authors.forename: Songee
authors.initials: S
authors.lastname: Branch
authors.forename: Tim
authors.initials: T
authors.lastname: Roach
authors.forename: Mina
authors.initials: M
authors.lastname: John
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.forename: Anthony
authors.initials: A
authors.lastname: Ogwu
authors.forename: Roger
authors.initials: R
authors.lastname: Shapiro
authors.forename: Julia G
authors.initials: JG
authors.lastname: Prado
authors.forename: Sarah
authors.initials: S
authors.lastname: Fidler
authors.forename: Jonathan
authors.initials: J
authors.lastname: Weber
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Pybus
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.forename: Rodney
authors.initials: R
authors.lastname: Phillips
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Philip
authors.initials: P
authors.lastname: Goulder
mesh_terms: D000483:Alleles; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015488:HIV Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D038622:Internationality; D007962:Leukocytes / Q000276:immunology*; D011110:Polymorphism, Genetic; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D015235:HLA-B Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus