title: The hepatitis C virus (HCV)-Trimera mouse: a model for evaluation of agents against HCV.
abstract: The lack of small-animal models that are suitable for evaluation of agents used to treat infection with hepatitis C virus (HCV) severely hinders the assessment of potential new therapies for the disease. This study created such a model, termed the "HCV-Trimera" model. The HCV-Trimera model was developed by using lethally irradiated mice, reconstituted with SCID mouse bone marrow cells, in which human liver fragments infected ex vivo with HCV had been transplanted. Viremia (positive-strand HCV RNA levels) in HCV-Trimera mice peaked at approximately day 18 after liver transplantation, and an infection rate of 85% was reached. Viral replication in liver grafts was evidenced by the presence of specific negative-strand HCV RNA. The usefulness of this model for evaluation of anti-HCV agents was demonstrated by the ability of a small molecule (an HCV internal ribosomal entry site inhibitor) and an anti-HCV human monoclonal antibody (HCV AB(XTL)68) to reduce virus loads in HCV-Trimera mice in a dose-dependent manner.
authors.affiliation: XTL Biopharmaceuticals, Rehovot, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Ilan
authors.forename: Joseph
authors.initials: J
authors.lastname: Arazi
authors.forename: Ofer
authors.initials: O
authors.lastname: Nussbaum
authors.forename: Arie
authors.initials: A
authors.lastname: Zauberman
authors.forename: Rachel
authors.initials: R
authors.lastname: Eren
authors.forename: Ido
authors.initials: I
authors.lastname: Lubin
authors.forename: Lewis
authors.initials: L
authors.lastname: Neville
authors.forename: Ofer
authors.initials: O
authors.lastname: Ben-Moshe
authors.forename: Alberto
authors.initials: A
authors.lastname: Kischitzky
authors.forename: Amir
authors.initials: A
authors.lastname: Litchi
authors.forename: Ido
authors.initials: I
authors.lastname: Margalit
authors.forename: Judith
authors.initials: J
authors.lastname: Gopher
authors.forename: Samir
authors.initials: S
authors.lastname: Mounir
authors.forename: Weizhong
authors.initials: W
authors.lastname: Cai
authors.forename: Nili
authors.initials: N
authors.lastname: Daudi
authors.forename: Ahamed
authors.initials: A
authors.lastname: Eid
authors.forename: Oded
authors.initials: O
authors.lastname: Jurim
authors.forename: Abraham
authors.initials: A
authors.lastname: Czerniak
authors.forename: Eithan
authors.initials: E
authors.lastname: Galun
authors.forename: Shlomo
authors.initials: S
authors.lastname: Dagan
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006526:Hepatitis C / Q000188:drug therapy* / Q000209:etiology / Q000821:virology; D006801:Humans; D008099:Liver / Q000821:virology; D051379:Mice; D012367:RNA, Viral / Q000097:blood; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral