Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models

TY - JOUR

T1 - Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models

AU - Bukh, Jens

AU - Meuleman, Philip

AU - Tellier, Raymond

AU - Engle, Ronald E

AU - Feinstone, Stephen M

AU - Eder, Gerald

AU - Satterfield, William C

AU - Govindarajan, Sugantha

AU - Krawczynski, Krzysztof

AU - Miller, Roger H

AU - Leroux-Roels, Geert

AU - Purcell, Robert H

PY - 2010/5/1

Y1 - 2010/5/1

N2 - 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 >104.7 IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 103-105 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 lb 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.

AB - 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 >104.7 IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 103-105 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 lb 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.

KW - Animals

KW - Cells, Cultured

KW - Chimera

KW - Disease Models, Animal

KW - Genotype

KW - Hepacivirus

KW - Hepatitis C

KW - Humans

KW - Liver

KW - Mice

KW - Mice, SCID

KW - Pan troglodytes

U2 - 10.1086/651579

DO - 10.1086/651579

M3 - Journal article

C2 - 20353362

SN - 0022-1899

VL - 201

SP - 1381

EP - 1389

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 9

ER -