title: Pol I-transcribed hepatitis C virus genome RNA replicates, produces an infectious virus and leads to severe hepatic steatosis in transgenic mice.
abstract: Patients chronically infected with hepatitis C virus (HCV) are at risk of developing end-stage liver disease and hepatocellular carcinoma. Development of drugs to inhibit hepatocyte damage and a vaccine against HCV is hampered by the lack of a small animal model. We generated mice in which the viral genome RNA was always present in the hepatocytes using a special transgene. Here we show that the HCV genome RNA transcribed by Pol I polymerase can replicate and produce infectious viruses in mice. We obtained a transgenic mouse with 200 copies per haploid which we named the A line mouse. It produced ~ 3 × 10(6) HCV RNA copies/mL serum, which is at the comparable level as patients with chronic HCV infection. This mouse was immunotolerant to HCV and showed hepatic steatosis without any necroinflammation at the age of 6 months or hepatocellular carcinoma at the age of 15 months. Thus, the A line mouse can be used as an animal model for chronic HCV infection. This will enable better study of the abnormalities in metabolism and signal transduction in infected hepatocytes, and development of drugs that cure abnormalities.
authors.affiliation: Department of Biochemistry, Hamamatsu University School of Medicine.
authors.forename: Mohammod Johirul
authors.initials: MJ
authors.lastname: Islam
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hikosaka
authors.forename: Hidenao
authors.initials: H
authors.lastname: Noritake
authors.forename: Mohammad Khaja Mafij
authors.initials: MK
authors.lastname: Uddin
authors.forename: Mohammed Badrul
authors.initials: MB
authors.lastname: Amin
authors.forename: Kazushi
authors.initials: K
authors.lastname: Aoto
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Wu
authors.forename: Eiji
authors.initials: E
authors.lastname: Sato
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miura
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology* / Q000473:pathology; D016679:Genome, Viral; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000150:complications* / Q000821:virology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D012318:RNA Polymerase I / Q000378:metabolism; D012367:RNA, Viral; D013997:Time Factors; D014158:Transcription, Genetic; D019562:Viral Load; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D012318:RNA Polymerase I