Expression of human CD81 in transgenic mice does not confer susceptibility to hepatitis C virus infection.
We previously demonstrated that hepatitis C virus (HCV) binds to human CD81 through the E2 glycoprotein. Therefore, expression of the human CD81 molecule in transgenic mice was expected to provide a new tool to study HCV infection in vivo, as the chimpanzee is the only species currently available as a laboratory animal model that can be infected with HCV. We produced transgenic mice expressing the human CD81 protein in a wide variety of tissues. We confirmed binding of recombinant E2 glycoprotein to the liver tissue as well as to thymocytes and splenic lymphocytes in the transgenic mice. We inoculated chimpanzee plasma infected with HCV into these animals. None of these transgenic animals showed evidence of viral replication. Furthermore, human CD81 transgenic mice that lack expression of endogenous mouse CD81 were also resistant to HCV infection. We conclude that expression of human CD81 alone is insufficient to confer susceptibility to HCV infection in the mouse. The presence of additional possible factors for HCV infection is discussed.
Masciopinto
Francesca
F
Department of Immunology, IRIS, Chiron SpA, I-53100, Siena, Italy.
Freer
Giulia
G
Burgio
Vito L
VL
Levy
Shoshana
S
Galli-Stampino
Luisa
L
Bendinelli
Mauro
M
Houghton
Michael
M
Abrignani
Sergio
S
Uematsu
Yasushi
Y
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D004198:Disease Susceptibility; D006526:Hepatitis C / Q000209:etiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins / Q000378:metabolism; D014779:Virus Replication
D015703:Antigens, CD; C554798:CD81 protein, human; C554799:Cd81 protein, mouse; D008565:Membrane Proteins; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus