Primary hepatocytes of Tupaia belangeri as a potential model for hepatitis C virus infection.
Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide, but the study of HCV infection has been hampered by the lack of an in vitro or in vivo small animal model. The tree shrew Tupaia belangeri is susceptible to infection with a variety of human viruses in vivo, including hepatitis viruses. We show that primary Tupaia hepatocytes can be infected with serum- or plasma-derived HCV from infected humans, as measured by de novo synthesis of HCV RNA, analysis of viral quasispecies evolution, and detection of viral proteins. Production of infectious virus could be demonstrated by passage to naive hepatocytes. To assess whether viral entry in Tupaia hepatocytes was dependent on the recently isolated HCV E2 binding protein CD81, we identified and characterized Tupaia CD81. Sequence analysis of cloned Tupaia cDNA revealed a high degree of homology between Tupaia and human CD81 large extracellular loops (LEL). Cellular binding of E2 and HCV infection could not be inhibited by anti-CD81 antibodies or soluble CD81-LEL, suggesting that viral entry can occur through receptors other than CD81. Thus, primary Tupaia hepatocytes provide a potential model for the study of HCV infection of hepatocytes.
Zhao
Xiping
X
Department of Medicine II, University of Freiburg, Freiburg, Germany.
Tang
Zhen-Ya
ZY
Klumpp
Bettina
B
Wolff-Vorbeck
Guido
G
Barth
Heidi
H
Levy
Shoshana
S
von Weizsäcker
Fritz
F
Blum
Hubert E
HE
Baumert
Thomas F
TF
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D006801:Humans; D008565:Membrane Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis; D011991:Receptors, Virus / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D060225:Tetraspanin 28; D014417:Tupaia; D014759:Viral Envelope Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis
D015703:Antigens, CD; C554798:CD81 protein, human; D018076:DNA, Complementary; D008565:Membrane Proteins; D012367:RNA, Viral; D011991:Receptors, Virus; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C091015:glycoprotein E2, Hepatitis C virus