Pathogenesis of hepatitis C virus infection in Tupaia belangeri.
The lack of a small-animal model has hampered the analysis of hepatitis C virus (HCV) pathogenesis. The tupaia (Tupaia belangeri), a tree shrew, has shown susceptibility to HCV infection and has been considered a possible candidate for a small experimental model of HCV infection. However, a longitudinal analysis of HCV-infected tupaias has yet to be described. Here, we provide an analysis of HCV pathogenesis during the course of infection in tupaias over a 3-year period. The animals were inoculated with hepatitis C patient serum HCR6 or viral particles reconstituted from full-length cDNA. In either case, inoculation caused mild hepatitis and intermittent viremia during the acute phase of infection. Histological analysis of infected livers revealed that HCV caused chronic hepatitis that worsened in a time-dependent manner. Liver steatosis, cirrhotic nodules, and accompanying tumorigenesis were also detected. To examine whether infectious virus particles were produced in tupaia livers, naive animals were inoculated with sera from HCV-infected tupaias, which had been confirmed positive for HCV RNA. As a result, the recipient animals also displayed mild hepatitis and intermittent viremia. Quasispecies were also observed in the NS5A region, signaling phylogenic lineage from the original inoculating sequence. Taken together, these data suggest that the tupaia is a practical animal model for experimental studies of HCV infection.
Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan.
Yutaka
Y
Amako
Kyoko
K
Tsukiyama-Kohara
Asao
A
Katsume
Yuichi
Y
Hirata
Satoshi
S
Sekiguchi
Yoshimi
Y
Tobita
Yukiko
Y
Hayashi
Tsunekazu
T
Hishima
Nobuaki
N
Funata
Hiromichi
H
Yonekawa
Michinori
M
Kohara
D000818:Animals; D004195:Disease Models, Animal; D016174:Hepacivirus; D006526:Hepatitis C; D006651:Histocytochemistry; D006801:Humans; D008107:Liver Diseases / Q000473:pathology / Q000821:virology; D008137:Longitudinal Studies; D014417:Tupaia / Q000821:virology*; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014766:Viremia; D012324:RNA-Dependent RNA Polymerase
D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase