期刊
JOURNAL OF INFECTIOUS DISEASES
卷 201, 期 9, 页码 1381-1389出版社
OXFORD UNIV PRESS INC
DOI: 10.1086/651579
关键词
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资金
- National Institute of Allergy and Infectious Diseases, National Institutes of Health [N01-A0-2713]
- University of Copenhagen
- Lundbeck Foundation
- Ghent University [01G00507]
- Belgian State via the Interuniversity Attraction Poles Program [P6/36 HEPRO]
- European Union
- Research Foundation Flanders (FWO-Vlaanderen)
Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >10(4.7) IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 10(3)-10(5) chimpanzee infectious doses/mL. Human liver-chimeric mice developed high-titer infections after inoculation with the challenge viruses of genotypes 1-6. Inoculation studies with different doses of the genotype 1b pool suggested that a relatively high virus dose is required to consistently infect chimeric mice. The challenge pools represent a unique resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo.
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