Challenge Pools of Hepatitis C Virus Genotypes 1-6 Prototype Strains: Replication Fitness and Pathogenicity in Chimpanzees and Human Liver-Chimeric Mouse Models.

Authors

Bukh J, Meuleman P, Tellier R, Engle RE, Feinstone SM, Eder G, Satterfield WC, Govindarajan S, Krawczynski K, Miller RH, Leroux-Roels G, Purcell RH.

Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and 2Divisions of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland; 3Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, M. D. Anderson Cancer Center, Bastrop, Texas; 4Liver Research Laboratory, Rancho Los Amigos Medical Center, Downey, California; 5Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia; 6Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Copenhagen University Hospital, Hvidovre, and Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; 7Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium; 8Karl Landsteiner Institute of Epidemiology of Infectious Disorders and Vaccination, St. Pölten, Austria.

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.

References

Bukh J, Meuleman P, Tellier R, Engle RE, Feinstone SM, Eder G, Satterfield WC, Govindarajan S, Krawczynski K, Miller RH, Leroux-Roels G, Purcell RH. Challenge Pools of Hepatitis C Virus Genotypes 1-6 Prototype Strains: Replication Fitness and Pathogenicity in Chimpanzees and Human Liver-Chimeric Mouse Models. J. Infect. Dis. 2010
PubMed id : 20353362
doi : 10.1086/651579

Link to pubmed | Link to Google Scholar | Link to full text publication

2010

The Journal of infectious diseases

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