Molecular Biology of Hepatitis C Virus

Miller, R H.

Abstract

Hepatitis C virus (HCV) is an important human pathogen that is strongly associated with post transfusion hepatitis as well as sporadic non-A, non-B hepatitis. Recently, HCV cDNA was cloned and its genome sequenced by others. A region of the predicted polyprotein sequence was found to share similarity with a non-structural protein encoded by dengue virus, a member of the flavivirus family. We found, using computer-assisted analysis, that HCV shares an even greater degree of protein sequence similarity with members of the pestivirus group (i.e., bovine viral diarrhea virus and hog cholera virus) which are thought to be distantly related to the flaviviruses. In addition, we found that HCV shares significant protein sequence similarity with the polyproteins encoded by members of the picornavirus-like and alphavirus-like plant virus supergroups. These data suggest that HCV may be evolutionarily related to both plant and animal viruses. PCR amplification was used to study the pathogenesis of HCV infection in patients and experimentally infected primates. An unexpected finding was the observation that HCV replication begins as early as three days following experimental infection of chimpanzees.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000570-01
• Application #: 3809732
• Support Year: 1
• Fiscal Year: 1990

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

Kyuregyan, Karen K; Poleschuk, Valentina F; Zamyatina, Natalya A et al. (2005) Acute GB virus B infection of marmosets is accompanied by mutations in the NS5A protein. Virus Res 114:154-7

Meunier, Jean-Christophe; Engle, Ronald E; Faulk, Kristina et al. (2005) Evidence for cross-genotype neutralization of hepatitis C virus pseudo-particles and enhancement of infectivity by apolipoprotein C1. Proc Natl Acad Sci U S A 102:4560-5

Bukh, Jens (2004) A critical role for the chimpanzee model in the study of hepatitis C. Hepatology 39:1469-75

Nam, Jae-Hwan; Faulk, Kristina; Engle, Ronald E et al. (2004) In vivo analysis of the 3' untranslated region of GB virus B after in vitro mutagenesis of an infectious cDNA clone: persistent infection in a transfected tamarin. J Virol 78:9389-99

Bukh, Jens; Christensen, Erik; Krogsgaard, Kim (2003) [Treatment and prevention of hepatitis C--progress and challenges. The Danish Society of Hepatology] Ugeskr Laeger 165:1233

Sakai, Akito; Claire, Marisa St; Faulk, Kristina et al. (2003) The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences. Proc Natl Acad Sci U S A 100:11646-51

Bartosch, Birke; Bukh, Jens; Meunier, Jean-Christophe et al. (2003) In vitro assay for neutralizing antibody to hepatitis C virus: evidence for broadly conserved neutralization epitopes. Proc Natl Acad Sci U S A 100:14199-204

Corbet, Sylvie; Bukh, Jens; Heinsen, Anja et al. (2003) Hepatitis C virus subtyping by a core-envelope 1-based reverse transcriptase PCR assay with sequencing and its use in determining subtype distribution among Danish patients. J Clin Microbiol 41:1091-100

Bukh, Jens; Pietschmann, Thomas; Lohmann, Volker et al. (2002) Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees. Proc Natl Acad Sci U S A 99:14416-21

Ma, Xiaoying; Forns, Xavier; Gutierrez, Robin et al. (2002) DNA-based vaccination against hepatitis C virus (HCV): effect of expressing different forms of HCV E2 protein and use of CpG-optimized vectors in mice. Vaccine 20:3263-71