title: Expression of human CD81 in transgenic mice does not confer susceptibility to hepatitis C virus infection.
abstract: 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.
authors.affiliation: Department of Immunology, IRIS, Chiron SpA, I-53100, Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Masciopinto
authors.forename: Giulia
authors.initials: G
authors.lastname: Freer
authors.forename: Vito L
authors.initials: VL
authors.lastname: Burgio
authors.forename: Shoshana
authors.initials: S
authors.lastname: Levy
authors.forename: Luisa
authors.initials: L
authors.lastname: Galli-Stampino
authors.forename: Mauro
authors.initials: M
authors.lastname: Bendinelli
authors.forename: Michael
authors.initials: M
authors.lastname: Houghton
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Uematsu
mesh_terms: 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
chemical_list: 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