Hepatitis C virus JFH-1 strain infection in chimpanzees is associated with low pathogenicity and emergence of an adaptive mutation.

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Takanobu KatoT Jake Liang

Abstract

The identification of the hepatitis C virus (HCV) strain JFH-1 enabled the successful development of infectious cell culture systems. Although this strain replicates efficiently and produces infectious virus in cell culture, the replication capacity and pathogenesis in vivo are still undefined. To assess the in vivo phenotype of the JFH-1 virus, cell culture-generated JFH-1 virus (JFH-1cc) and patient serum from which JFH-1 was isolated were inoculated into chimpanzees. Both animals became HCV RNA-positive 3 days after inoculation but showed low-level viremia and no evidence of hepatitis. HCV viremia persisted 8 and 34 weeks in JFH-1cc and patient serum-infected chimpanzees, respectively. Immunological analysis revealed that HCV-specific immune responses were similarly induced in both animals. Sequencing of HCV at various times of infection indicated more substitutions in the patient serum-inoculated chimpanzee, and the higher level of sequence variations seemed to be associated with a prolonged infection in this animal. A common mutation G838R in the NS2 region emerged early in both chimpanzees. This mutation enhances viral assembly, leading to an increase in viral production in transfected or infected cells. Our study shows t...Continue Reading

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Citations

Jun 29, 2013·Biochemical and Biophysical Research Communications·Hisashi IshidaTetsuo Takehara
Jul 13, 2012·Journal of Virology·Tomoko DateTakaji Wakita
Jul 23, 2013·PloS One·Yoshihiro MatsumotoHideki Aizaki
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Feb 18, 2011·Journal of Gastroenterology·Angela Dolganiuc, Gyongyi Szabo
Jun 15, 2011·Biochemical and Biophysical Research Communications·Yuka OkamotoTakanobu Kato
Jun 16, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Heidi BarthT Jake Liang
Feb 11, 2012·Microbiology and Immunology·Tomoko DateTakaji Wakita
Apr 11, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Takuya MatsumuraMichio Imawari
May 4, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mohsan SaeedTakanobu Kato
Mar 30, 2012·The Journal of General Virology·Midori TakedaNobuyuki Kato
May 10, 2011·Vaccine·Daisuke AkazawaTakaji Wakita
Dec 21, 2019·The Journal of General Virology·Noriyuki WatanabeTakaji Wakita
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Sep 11, 2019·Cold Spring Harbor Perspectives in Medicine·Takaji Wakita
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Oct 20, 2020·Journal of Alzheimer's Disease : JAD·Michael R DugganKamel Khalili
Sep 23, 2021·The New England Journal of Medicine·T Jake LiangCharles M Rice

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