Establishment of an infectious genotype 1b hepatitis C virus clone in human hepatocyte chimeric mice.

نویسندگان

  • Takashi Kimura
  • Michio Imamura
  • Nobuhiko Hiraga
  • Tsuyoshi Hatakeyama
  • Daiki Miki
  • Chiemi Noguchi
  • Nami Mori
  • Masataka Tsuge
  • Shoichi Takahashi
  • Yoshifumi Fujimoto
  • Eiji Iwao
  • Hidenori Ochi
  • Hiromi Abe
  • Toshiro Maekawa
  • Keiko Arataki
  • Chise Tateno
  • Katsutoshi Yoshizato
  • Takaji Wakita
  • Toru Okamoto
  • Yoshiharu Matsuura
  • Kazuaki Chayama
چکیده

The establishment of clonal infection of hepatitis C virus (HCV) in a small-animal model is important for the analysis of HCV virology. A previous study developed models of molecularly cloned genotype 1a and 2a HCV infection using human hepatocyte-transplanted chimeric mice. This study developed a new model of molecularly cloned genotype 1b HCV infection. A full-length genotype 1b HCV genome, HCV-KT9, was cloned from a serum sample from a patient with severe acute hepatitis. The chimeric mice were inoculated intrahepatically with in vitro-transcribed HCV-KT9 RNA. Inoculated mice developed viraemia at 2 weeks post-infection, and this persisted for more than 6 weeks. Passage experiments indicated that the sera of these mice contained infectious HCV. Interestingly, a similar clone, HCV-KT1, in which the poly(U/UC) tract was 29 nt shorter than in HCV-KT9, showed poorer in vivo infectivity and replication ability. An in vitro study showed that no virus was produced in the culture medium from HCV-KT9-transfected cells. In conclusion, this study developed a genetically engineered genotype 1b HCV-infected mouse. This mouse model will be useful for the study of HCV virology, particularly the mechanism underlying the variable resistance of HCV genotypes to interferon therapy.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Baseline quasispecies selection and novel mutations contribute to emerging resistance-associated substitutions in hepatitis C virus after direct-acting antiviral treatment

Resistance-associated substitutions (RASs) in hepatitis C virus (HCV) appear upon failure of treatment with direct-acting antivirals (DAAs). However, their origin has not been clarified in detail. Among 11 HCV genotype 1b patients who experienced virologic failure with asunaprevir (ASV)/daclatasvir (DCV), 10 had major NS5A L31M/V-Y93H variants after treatment. L31M/V-Y93H variants were detected...

متن کامل

Epidemiologic Study of Hepatitis C Virus Transmission in Lorestan Province (2011-14)

ABSTRACT        Background and Objective: This study was conducted to evaluate epidemiology of risk factors for hepatitis C virus (HCV) transmission, and determine the association of its genotypes with viral load and response to treatment in patients referred to the Infectious Disease Clinic of Khorramabad.         Methods...

متن کامل

Establishment of NS3 tumor cell line expressing Hepatitis C virus Non-structural Protein 3 as valuable tool for HCV challenging in mice

Introduction: Hepatitis C virus (HCV) is one of the major medical problems. Human and chimpanzees are the only specific hosts which are naturally susceptible to HCV infection. Mice and other common laboratory animals are resistant to the virus, hence HCV prophylactic and therapeutic researches are very difficult and challenging. HCV non-structural protein 3 (NS3) is one of the most attractive t...

متن کامل

Amino Acid Polymorphisms in Hepatitis C Virus Core Affect Infectious Virus Production and Major Histocompatibility Complex Class I Molecule Expression

Amino acid (aa) polymorphisms in the hepatitis C virus (HCV) genotype 1b core protein have been reported to be a potent predictor for poor response to interferon (IFN)-based therapy and a risk factor for hepatocarcinogenesis. We investigated the effects of these polymorphisms with genotype 1b/2a chimeric viruses that contained polymorphisms of Arg/Gln at aa 70 and Leu/Met at aa 91. We found tha...

متن کامل

Detection of Pre-treatment mutations leading to resistance to direct hepatitis C virus blocking drugs in patients with chronic hepatitis C

Background and objective: Human is the only host of hepatitis C virus. This virus has a positive single stranded RNA and lipoprotein envelop that has 7 confirmed genotypes. According to studies, genotypes 1a, 3a and 1b are the most common genotypes in Iran. No effective vaccine against HCV infection has been developed instead, advances in antiviral treatment using drugs that directly affect spe...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of general virology

دوره 89 Pt 9  شماره 

صفحات  -

تاریخ انتشار 2008