Divergent and convergent evolution after a common-source outbreak of hepatitis C virus.
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Date
2005-06
Authors
Ray, Stuart C.
Fanning, Liam J.
Wang, Xiao-Hong
Netski, Dale M.
Kenny-Walsh, Elizabeth
Thomas, David L.
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© 2005 Rockefeller University Press
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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.
Description
Keywords
Virus , Hepatitis C , Divergent evolution , Convergent evolution , Genomic sequence , Vaccine , Women , Outbreak
Citation
Ray SC, Fanning L, Wang XH, Netski DM, Kenny-Walsh E, Thomas DL (2005) 'Divergent and convergent evolution after a common-source outbreak of hepatitis C virus'. The Journal of experimental medicine, 201 (11):1753-1759. doi: 10.1084/jem.20050122