Compensatory mutation partially restores fitness and delays reversion of escape mutation within the immunodominant HLA-B*5703-restricted Gag epitope in chronic human immunodeficiency virus type 1 infection.
HLA-B*5703 is associated with effective immune control in human immunodeficiency virus type 1 (HIV-1) infection. Here we describe an escape mutation within the immunodominant HLA-B*5703-restricted epitope in chronic HIV-1 infection, KAFSPEVIPMF (Gag 162-172), and demonstrate that this mutation reduces viral replicative capacity. Reversion of this mutation following transmission to HLA-B*5703-negative recipients was delayed by the compensatory mutation S165N within the same epitope. These data may help explain the observed association between HLA-B*5703 and long-term control of viremia.
Crawford
Hayley
H
Department of Pediatrics, University of Oxford, Peter Medawar Building for Pathogen Research, South Parks Rd., Oxford OX1 3SY, United Kingdom.
Prado
Julia G
JG
Leslie
Alasdair
A
Hué
Stéphane
S
Honeyborne
Isobella
I
Reddy
Sharon
S
van der Stok
Mary
M
Mncube
Zenele
Z
Brander
Christian
C
Rousseau
Christine
C
Mullins
James I
JI
Kaslow
Richard
R
Goepfert
Paul
P
Allen
Susan
S
Hunter
Eric
E
Mulenga
Joseph
J
Kiepiela
Photini
P
Walker
Bruce D
BD
Goulder
Philip J R
PJ
D000595:Amino Acid Sequence; D015683:Gene Products, gag / Q000145:classification / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes; D016013:Likelihood Functions; D009154:Mutation; D010802:Phylogeny; D014779:Virus Replication
D015683:Gene Products, gag; D015235:HLA-B Antigens; D016056:Immunodominant Epitopes