• Open Access

Effect of immune pressure on hepatitis C virus evolution: Insights from a single-source outbreak§

Authors

  • Shahzma Merani,

    1. Centre for Forensic Science, University of Western Australia, Western Australia, Australia
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  • Danijela Petrovic,

    1. Department of Clinical Medicine and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland
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  • Ian James,

    1. Centre for Clinical Immunology and Biomedical Statistics, Institute of Immunology and Infectious Disease, Murdoch University, Western Australia, Australia
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  • Abha Chopra,

    1. Centre for Clinical Immunology and Biomedical Statistics, Institute of Immunology and Infectious Disease, Murdoch University, Western Australia, Australia
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  • Don Cooper,

    1. Centre for Clinical Immunology and Biomedical Statistics, Institute of Immunology and Infectious Disease, Murdoch University, Western Australia, Australia
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  • Elizabeth Freitas,

    1. Centre for Clinical Immunology and Biomedical Statistics, Institute of Immunology and Infectious Disease, Murdoch University, Western Australia, Australia
    Current affiliation:
    1. Conexio Genomics, Western Australia, Australia
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  • Andri Rauch,

    1. University Clinic of Infectious Diseases, University Hospital Bern and University of Bern, Bern, Switzerland
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  • Julia di Iulio,

    1. Institute of Microbiology, University Hospital Center, University of Lausanne, Lausanne, Switzerland
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  • Mina John,

    1. Centre for Clinical Immunology and Biomedical Statistics, Institute of Immunology and Infectious Disease, Murdoch University, Western Australia, Australia
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  • Michaela Lucas,

    1. Centre for Clinical Immunology and Biomedical Statistics, Institute of Immunology and Infectious Disease, Murdoch University, Western Australia, Australia
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  • Karen Fitzmaurice,

    1. Department of Clinical Medicine and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland
    2. Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom
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  • Susan McKiernan,

    1. Department of Clinical Medicine and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland
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  • Suzanne Norris,

    1. Department of Clinical Medicine and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland
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  • Dermot Kelleher,

    1. Department of Clinical Medicine and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland
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  • Paul Klenerman,

    1. Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom
    2. Biomedical Research Centre, John Radcliffe Hospital, Oxford, United Kingdom
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  • Silvana Gaudieri

    Corresponding author
    1. Centre for Forensic Science, University of Western Australia, Western Australia, Australia
    2. Centre for Clinical Immunology and Biomedical Statistics, Institute of Immunology and Infectious Disease, Murdoch University, Western Australia, Australia
    3. School of Anatomy and Human Biology, University of Western Australia, Western Australia, Australia
    • School of Anatomy and Human Biology, University of Western Australia, Mailbag M420, 35 Stirling Highway, Crawley 6009, Western Australia, Australia
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    • fax: 61-8-9224 1981


  • The hepatitis C virus sequences described in this article have been submitted to GenBank with the following accession numbers: HM106522 to HM106981 and HQ399442-HQ399454.

  • Potential conflict of interest: Dr. Freitas is an employee of Conexio Genomics.

  • §

    Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms

Abstract

The host's immune response to hepatitis C virus (HCV) can result in the selection of characteristic mutations (adaptations) that enable the virus to escape this response. The ability of the virus to mutate at these sites is dependent on the incoming virus, the fitness cost incurred by the mutation, and the benefit to the virus in escaping the response. Studies examining viral adaptation in chronic HCV infection have shown that these characteristic immune escape mutations can be observed at the population level as human leukocyte antigen (HLA)–specific viral polymorphisms. We examined 63 individuals with chronic HCV infection who were infected from a single HCV genotype 1b source. Our aim was to determine the extent to which the host's immune pressure affects HCV diversity and the ways in which the sequence of the incoming virus, including preexisting escape mutations, can influence subsequent mutations in recipients and infection outcomes. Conclusion: HCV sequences from these individuals revealed 29 significant associations between specific HLA types within the new hosts and variations within their viruses, which likely represent new viral adaptations. These associations did not overlap with previously reported adaptations for genotypes 1a and 3a and possibly reflected a combination of constraint due to the incoming virus and genetic distance between the strains. However, these sites accounted for only a portion of the sites in which viral diversity was observed in the new hosts. Furthermore, preexisting viral adaptations in the incoming (source) virus likely influenced the outcomes in the new hosts. (HEPATOLOGY 2011;53:396-405)

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