Adaptation of HIV-1 to human leukocyte antigen class I.
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.
Kawashima
Yuka
Y
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Pfafferott
Katja
K
Frater
John
J
Matthews
Philippa
P
Payne
Rebecca
R
Addo
Marylyn
M
Gatanaga
Hiroyuki
H
Fujiwara
Mamoru
M
Hachiya
Atsuko
A
Koizumi
Hirokazu
H
Kuse
Nozomi
N
Oka
Shinichi
S
Duda
Anna
A
Prendergast
Andrew
A
Crawford
Hayley
H
Leslie
Alasdair
A
Brumme
Zabrina
Z
Brumme
Chanson
C
Allen
Todd
T
Brander
Christian
C
Kaslow
Richard
R
Tang
James
J
Hunter
Eric
E
Allen
Susan
S
Mulenga
Joseph
J
Branch
Songee
S
Roach
Tim
T
John
Mina
M
Mallal
Simon
S
Ogwu
Anthony
A
Shapiro
Roger
R
Prado
Julia G
JG
Fidler
Sarah
S
Weber
Jonathan
J
Pybus
Oliver G
OG
Klenerman
Paul
P
Ndung'u
Thumbi
T
Phillips
Rodney
R
Heckerman
David
D
Harrigan
P Richard
PR
Walker
Bruce D
BD
Takiguchi
Masafumi
M
Goulder
Philip
P
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
D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D015235:HLA-B Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus