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Divergent and convergent evolution after a common-source outbreak of hepatitis C virus

By Stuart C. Ray, Liam Fanning, Xiao-Hong Wang, Dale M. Netski, Elizabeth Kenny-Walsh and David L. Thomas

Abstract

The genomic sequences of viruses that are highly mutable and cause chronic infection tend to diverge over time. We report that these changes represent both immune-driven selection and, in the absence of immune pressure, reversion toward an ancestral consensus. Sequence changes in hepatitis C virus (HCV) structural and nonstructural genes were studied in a cohort of women accidentally infected with HCV in a rare common-source outbreak. We compared sequences present in serum obtained 18–22 yr after infection to sequences present in the shared inoculum and found that HCV evolved along a distinct path in each woman. Amino acid substitutions in known epitopes were directed away from consensus in persons having the HLA allele associated with that epitope (immune selection), and toward consensus in those lacking the allele (reversion). These data suggest that vaccines for genetically diverse viruses may be more effective if they represent consensus sequence, rather than a human isolate

Topics: Article
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2213258
Provided by: PubMed Central
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    Citations

    1. (2004). Accurate representation of the hepatitis C virus quasispecies in 5.2-kilobase amplicons.
    2. (1998). Acute hepatitis C virus structural gene sequences as predictors of persistent viremia: hypervariable region 1 as decoy.
    3. (2001). BioEdit: Biological sequence alignment editor for Windows 95/98/NT version
    4. (2004). CD8 epitope escape and reversion in acute HCV infection.
    5. (2002). Cellular immune responses against hepatitis C virus: the evidence base
    6. Cellular immune selection with hepatitis C virus persistence in humans.
    7. (2003). Changes in hypervariable region 1 of the envelope 2 glycoprotein of hepatitis C virus in children and adults with humoral immune defects.
    8. (1999). Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin.
    9. (2003). Consensus and ancestral state HIV vaccines.
    10. (2001). Conservation of the conformation and positive charges of hepatitis C virus E2 envelope glycoprotein hypervariable region 1 points to a role in cell attachment.
    11. (1997). Displaying the information contents of structural RNA alignments: the structure logos.
    12. (2002). Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level.
    13. (1998). Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy.
    14. (1992). Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution.
    15. (2004). HIV evolution: CTL escape mutation and reversion after transmission.
    16. (2000). Hypervariable region 1 sequence stability during hepatitis C virus replication in chimpanzees.
    17. (1997). Immunological significance of cytotoxic T lymphocyte epitope variants in patients chronically infected by the hepatitis C virus.
    18. (1998). Long-term evolution of the hypervariable region of hepatitis C virus in a common-source-infected cohort.
    19. (1998). MODELTEST: testing the model of DNA substitution.
    20. (1998). Multiple sequence alignment with Clustal X. Trends Biochem.
    21. (1991). Nucleotide sequence and mutation rate of the H strain of hepatitis C virus.
    22. (2004). Persistence of hepatitis C virus in a white population: associations with human leukocyte antigen class 1.
    23. (2003). Progressive reversion of human immunodeficiency virus type 1 resistance mutations in vivo after transmission of a multiply drug-resistant virus.
    24. Reversion of CTL escape-variant immunodeficiency viruses in vivo.
    25. (1990). Sequence logos: a new way to display consensus sequences. Nucleic Acids Res.
    26. (2000). Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia.
    27. The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes.

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