Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Journal of Infectious Diseases |
Volume | 201 |
Issue number | 9 |
Pages (from-to) | 1381-9 |
Number of pages | 9 |
ISSN | 0022-1899 |
DOIs | |
Publication status | Published - 1 May 2010 |
- Animals, Cells, Cultured, Chimera, Disease Models, Animal, Genotype, Hepacivirus, Hepatitis C, Humans, Liver, Mice, Mice, SCID, Pan troglodytes
Research areas
ID: 33951805