Challenge Pools of Hepatitis C Virus Genotypes 1–6 Prototype Strains: Replication Fitness and Pathogenicity in Chimpanzees and Human Liver–Chimeric Mouse Models
Year: 2010
Type: article
Abstract: 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.
DOI: 10.1086/651579
Institutions: University of Copenhagen, National Institutes of Health, Hvidovre Hospital, Copenhagen University Hospital, National Institute of Allergy and Infectious Diseases, Ghent University Hospital, Ghent University, Center for Biologics Evaluation and Research, United States Food and Drug Administration, The University of Texas MD Anderson Cancer Center, Rancho Los Amigos National Rehabilitation Center, Centers for Disease Control and Prevention
Language: English
Topic: Hepatitis C virus research
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2146782236