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    Rapid viral escape at an immunodominant simian-human immunodeficiency virus cytotoxic T-lymphocyte epitope exacts a dramatic fitness cost

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    Author
    Fernandez, CS; Stratov, I; De Rose, R; Walsh, K; Dale, CJ; Smith, MZ; Agy, MB; Hu, SL; Krebs, K; Watkins, DI; ...
    Date
    2005-05-01
    Source Title
    JOURNAL OF VIROLOGY
    Publisher
    AMER SOC MICROBIOLOGY
    University of Melbourne Author/s
    Fernandez, Caroline; STRATOV, IVAN; De Rose, Robert; Walsh, Katrina; Kent, Stephen; Batten, Caroline; Smith, Miranda
    Affiliation
    Microbiology And Immunology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Fernandez, C. S., Stratov, I., De Rose, R., Walsh, K., Dale, C. J., Smith, M. Z., Agy, M. B., Hu, S. L., Krebs, K., Watkins, D. I., O'Connor, D. H., Davenport, M. P. & Kent, S. J. (2005). Rapid viral escape at an immunodominant simian-human immunodeficiency virus cytotoxic T-lymphocyte epitope exacts a dramatic fitness cost. JOURNAL OF VIROLOGY, 79 (9), pp.5721-5731. https://doi.org/10.1128/JVI.79.9.5721-5731.2005.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/26297
    DOI
    10.1128/JVI.79.9.5721-5731.2005
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1082732
    Description

    C1 - Journal Articles Refereed

    Abstract
    Escape from specific T-cell responses contributes to the progression of human immunodeficiency virus type 1 (HIV-1) infection. T-cell escape viral variants are retained following HIV-1 transmission between major histocompatibility complex (MHC)-matched individuals. However, reversion to wild type can occur following transmission to MHC-mismatched hosts in the absence of cytotoxic T-lymphocyte (CTL) pressure, due to the reduced fitness of the escape mutant virus. We estimated both the strength of immune selection and the fitness cost of escape variants by studying the rates of T-cell escape and reversion in pigtail macaques. Near-complete replacement of wild-type with T-cell escape viral variants at an immunodominant simian immunodeficiency virus Gag epitope KP9 occurred rapidly (over 7 days) following infection of pigtail macaques with SHIVSF162P3. Another challenge virus, SHIVmn229, previously serially passaged through pigtail macaques, contained a KP9 escape mutation in 40/44 clones sequenced from the challenge stock. When six KP9-responding animals were infected with this virus, the escape mutation was maintained. By contrast, in animals not responding to KP9, rapid reversion of the K165R mutation occurred over 2 weeks after infection. The rapidity of reversion to the wild-type sequence suggests a significant fitness cost of the T-cell escape mutant. Quantifying both the selection pressure exerted by CTL and the fitness costs of escape mutation has important implications for the development of CTL-based vaccine strategies.
    Keywords
    Medical Virology ; Infectious Diseases

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