HIV evolution: CTL escape mutation and reversion after transmission.
Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 patients drawn from the B- and C-clade epidemics, focusing on human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801, which are associated with long-term HIV control and are therefore likely to exert strong selection pressure on the virus. The CTL response dominating acute infection in HLA-B57/5801-positive subjects drove positive selection of an escape mutation that reverted to wild-type after transmission to HLA-B57/5801-negative individuals. A second escape mutation within the epitope, by contrast, was maintained after transmission. These data show that the process of accumulation of escape mutations within HIV is not inevitable. Complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level.
Leslie
A J
AJ
Department of Pediatrics, Fuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
Pfafferott
K J
KJ
Chetty
P
P
Draenert
R
R
Addo
M M
MM
Feeney
M
M
Tang
Y
Y
Holmes
E C
EC
Allen
T
T
Prado
J G
JG
Altfeld
M
M
Brander
C
C
Dixon
C
C
Ramduth
D
D
Jeena
P
P
Thomas
S A
SA
St John
A
A
Roach
T A
TA
Kupfer
B
B
Luzzi
G
G
Edwards
A
A
Taylor
G
G
Lyall
H
H
Tudor-Williams
G
G
Novelli
V
V
Martinez-Picado
J
J
Kiepiela
P
P
Walker
B D
BD
Goulder
P J R
PJ
D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D000939:Epitopes; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000276:immunology / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D016013:Likelihood Functions; D009154:Mutation; D010802:Phylogeny; D012641:Selection, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load
D000939:Epitopes; D015235:HLA-B Antigens; C103707:HLA-B57 antigen