title: HIV evolution: CTL escape mutation and reversion after transmission.
abstract: 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.
authors.affiliation: Department of Pediatrics, Fuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Leslie
authors.forename: K J
authors.initials: KJ
authors.lastname: Pfafferott
authors.forename: P
authors.initials: P
authors.lastname: Chetty
authors.forename: R
authors.initials: R
authors.lastname: Draenert
authors.forename: M M
authors.initials: MM
authors.lastname: Addo
authors.forename: M
authors.initials: M
authors.lastname: Feeney
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.forename: E C
authors.initials: EC
authors.lastname: Holmes
authors.forename: T
authors.initials: T
authors.lastname: Allen
authors.forename: J G
authors.initials: JG
authors.lastname: Prado
authors.forename: M
authors.initials: M
authors.lastname: Altfeld
authors.forename: C
authors.initials: C
authors.lastname: Brander
authors.forename: C
authors.initials: C
authors.lastname: Dixon
authors.forename: D
authors.initials: D
authors.lastname: Ramduth
authors.forename: P
authors.initials: P
authors.lastname: Jeena
authors.forename: S A
authors.initials: SA
authors.lastname: Thomas
authors.forename: A
authors.initials: A
authors.lastname: St John
authors.forename: T A
authors.initials: TA
authors.lastname: Roach
authors.forename: B
authors.initials: B
authors.lastname: Kupfer
authors.forename: G
authors.initials: G
authors.lastname: Luzzi
authors.forename: A
authors.initials: A
authors.lastname: Edwards
authors.forename: G
authors.initials: G
authors.lastname: Taylor
authors.forename: H
authors.initials: H
authors.lastname: Lyall
authors.forename: G
authors.initials: G
authors.lastname: Tudor-Williams
authors.forename: V
authors.initials: V
authors.lastname: Novelli
authors.forename: J
authors.initials: J
authors.lastname: Martinez-Picado
authors.forename: P
authors.initials: P
authors.lastname: Kiepiela
authors.forename: B D
authors.initials: BD
authors.lastname: Walker
authors.forename: P J R
authors.initials: PJ
authors.lastname: Goulder
mesh_terms: 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
chemical_list: D000939:Epitopes; D015235:HLA-B Antigens; C103707:HLA-B57 antigen