Molecular evolution of GB virus B hepatitis virus during acute resolving and persistent infections in experimentally infected tamarins.
GB virus B (GBV-B) causes acute hepatitis in experimentally infected tamarins. We compared evolutionary features in acute resolving and persistent GBV-B infection. We detected no evidence of evolution in four animals with clearance during weeks 9-12, whereas three animals with clearance during weeks 13-26 had several substitutions in their polyprotein sequence. A single tamarin had long-term GBV-B viraemia; analysis of virus recovered at weeks 2, 5, 12, 20, 26, 52 and 104 demonstrated that mutations accumulated over time. Overall, the amino acid substitution rate was 3.5x10(-3) and 1.1x10(-3) substitutions per site year(-1) during weeks 1-52 and 53-104, respectively. Thus, there was a significant decrease in evolution over time, as found for hepatitis C virus. The rate of non-synonymous substitution per non-synonymous site compared with that of synonymous substitution per synonymous site decreased over time, suggesting reduction of positive selective pressure. These data demonstrate that prolonged GBV-B infection is associated with viral evolution.
Takikawa
Shingo
S
Hepatitis Viruses and Molecular Hepatitis Sections, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Engle
Ronald E
RE
Faulk
Kristina N
KN
Emerson
Suzanne U
SU
Purcell
Robert H
RH
Bukh
Jens
J
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D029406:GB virus B / Q000145:classification* / Q000235:genetics*; D015684:Gene Products, pol / Q000235:genetics; D006524:Hepatitis, Viral, Animal / Q000821:virology*; D051039:Leontopithecus; D008992:Monkey Diseases / Q000821:virology*
D015684:Gene Products, pol