Journal article
Passive Sexual Transmission of Human Immunodeficiency Virus Type 1 Variants and Adaptation in New Hosts
Journal of Virology, Vol.80(14), pp.7226-7234
2006
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.
Details
- Title
- Passive Sexual Transmission of Human Immunodeficiency Virus Type 1 Variants and Adaptation in New Hosts
- Authors/Creators
- A.J. Frater (Author/Creator) - Medawar Building for Pathogen ResearchC.T.T. Edwards (Author/Creator) - Medawar Building for Pathogen ResearchN. McCarthy (Author/Creator) - University of OxfordJ. Fox (Author/Creator) - Division of Medicine, Wright Fleming Institute, Imperial College, St. Mary's Hospital, 4th Floor, Norfolk Place, Paddington, London W2 1PG, United KingdomH. Brown (Author/Creator) - Medawar Building for Pathogen ResearchA. Milicic (Author/Creator) - Medawar Building for Pathogen ResearchN. Mackie (Author/Creator) - Division of Medicine, Wright Fleming Institute, Imperial College, St. Mary's Hospital, 4th Floor, Norfolk Place, Paddington, London W2 1PG, United KingdomT. Pillay (Author/Creator) - Medawar Building for Pathogen ResearchJ.W. Drijfhout (Author/Creator) - Leiden University Medical CenterS. Dustan (Author/Creator) - Division of Medicine, Wright Fleming Institute, Imperial College, St. Mary's Hospital, 4th Floor, Norfolk Place, Paddington, London W2 1PG, United KingdomJ.R. Clarke (Author/Creator) - Division of Medicine, Wright Fleming Institute, Imperial College, St. Mary's Hospital, 4th Floor, Norfolk Place, Paddington, London W2 1PG, United KingdomE.C. Holmes (Author/Creator) - University of OxfordH.T. Zhang (Author/Creator) - Medawar Building for Pathogen ResearchK. Pfafferott (Author/Creator) - Medawar Building for Pathogen ResearchP.J.R. Goulder (Author/Creator) - Medawar Building for Pathogen ResearchM.O. McClure (Author/Creator) - Division of Medicine, Wright Fleming Institute, Imperial College, St. Mary's Hospital, 4th Floor, Norfolk Place, Paddington, London W2 1PG, United KingdomJ. Weber (Author/Creator) - St Mary's HospitalR.E. Phillips (Author/Creator) - Medawar Building for Pathogen ResearchS. Fidler (Author/Creator) - St Mary's Hospital
- Publication Details
- Journal of Virology, Vol.80(14), pp.7226-7234
- Publisher
- American Society for Microbiology
- Identifiers
- 991005540374407891
- Copyright
- © American Society for Microbiology
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.46 HIV Pathogenesis
- Web Of Science research areas
- Virology
- ESI research areas
- Microbiology