title: Passive sexual transmission of human immunodeficiency virus type 1 variants and adaptation in new hosts.
abstract: Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle for the design of a successful vaccine. Certain viral polymorphisms encode human leukocyte antigen (HLA)-associated immune escape, potentially overcoming limited vaccine protection. Although transmission of immune escape variants has been reported, the overall extent to which this phenomenon occurs in populations and the degree to which it contributes to HIV-1 viral evolution are unknown. Selection on the HIV-1 env gene at transmission favors neutralization-sensitive variants, but it is not known to what degree selection acts on the internal HIV-1 proteins to restrict or enhance the transmission of immune escape variants. Studies have suggested that HLA class I may determine susceptibility to HIV-1 infection, but a definitive role for HLA at transmission remains unproven. Comparing populations of acute seroconverters and chronically infected patients, we found no evidence of selection acting to restrict transmission of HIV-1 variants. We found that statistical associations previously reported in chronic infection between viral polymorphisms and HLA class I alleles are not present in acute infection, suggesting that the majority of viral polymorphisms in these patients are the result of transmission rather than de novo adaptation. Using four episodes of HIV-1 transmission in which the donors and recipients were both sampled very close to the time of infection we found that, despite a transmission bottleneck, genetic variants of HIV-1 infection are transmitted in a frequency-dependent manner. As HIV-1 infections are seeded by unique donor-adapted viral variants, each episode is a highly individual antigenic challenge. Host-specific, idiosyncratic HIV-1 antigenic diversity will seriously tax the efficacy of immunization based on consensus sequences.
authors.affiliation: The James Martin 21st Century School, Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, United Kingdom.
authors.forename: A J
authors.initials: AJ
authors.lastname: Frater
authors.forename: C T T
authors.initials: CT
authors.lastname: Edwards
authors.forename: N
authors.initials: N
authors.lastname: McCarthy
authors.forename: J
authors.initials: J
authors.lastname: Fox
authors.forename: H
authors.initials: H
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Milicic
authors.forename: N
authors.initials: N
authors.lastname: Mackie
authors.forename: T
authors.initials: T
authors.lastname: Pillay
authors.forename: J W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: S
authors.initials: S
authors.lastname: Dustan
authors.forename: J R
authors.initials: JR
authors.lastname: Clarke
authors.forename: E C
authors.initials: EC
authors.lastname: Holmes
authors.forename: H T
authors.initials: HT
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Pfafferott
authors.forename: P J
authors.initials: PJ
authors.lastname: Goulder
authors.forename: M O
authors.initials: MO
authors.lastname: McClure
authors.forename: J
authors.initials: J
authors.lastname: Weber
authors.forename: R E
authors.initials: RE
authors.lastname: Phillips
authors.forename: S
authors.initials: S
authors.lastname: Fidler
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000208:Acute Disease; D000222:Adaptation, Physiological / Q000235:genetics / Q000276:immunology; D000328:Adult; D002908:Chronic Disease; D019143:Evolution, Molecular; D015686:Gene Products, env / Q000235:genetics* / Q000276:immunology; D005805:Genes, MHC Class I / Q000235:genetics / Q000276:immunology; D006679:HIV Seropositivity / Q000235:genetics* / Q000276:immunology / Q000628:therapy / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012641:Selection, Genetic
chemical_list: D016915:AIDS Vaccines; D015686:Gene Products, env; D006680:HLA Antigens