The Journal of Experimental Medicine
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Published 6 June 2005. doi:10.1084/jem.20050122
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 11, 1753-1759
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ARTICLE

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

Stuart C. Ray1, Liam Fanning2, Xiao-Hong Wang1,3, Dale M. Netski1, Elizabeth Kenny-Walsh2, and David L. Thomas1

1 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231
2 Hepatitis C Unit, Department of Medicine, Cork University Hospital, National University of Ireland, Cork, UK
3 Southwest Hospital, Third Military Medical University, Chongqinq, Peoples Republic of China 400038

CORRESPONDENCE Stuart C. Ray: sray{at}jhmi.edu

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.

Abbreviation used: HCV, hepatitis C virus.


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