Processing of hepatitis C virus core protein is regulated by its C-terminal sequence.
Polyprotein processing of plus-strand RNA viruses is important in the regulation of gene production and replication. The core protein of hepatitis C virus (HCV), constructing the viral particle, is processed from its precursor polyprotein and observed as two forms, p23 and p21. Production of p21 by cleavage at the C-terminus of p23 is considered crucial to viral assembly and replication. In this study, this processing step was compared between clones isolated from two patients with fulminant hepatitis and from five patients with chronic hepatitis by an in vitro translation assay and cell transfection assay. The p21 core protein was predominant from the clone isolated from one of the fulminant hepatitis patient (p21 core protein production was 65.98%), while p23 was abundant with clones from five chronic hepatitis patients (p21 core protein production was 7.11+/-1.62%) and clone from another fulminant hepatitis patient (p21 core protein production was 13.36%). Investigations with chimeric and mutation-introduced constructs revealed that four amino acid residues in the C-terminus of the core region are responsible for this difference. The data suggest that core protein processing is regulated by C-terminus mutations.
Kato
Takanobu
T
Department of Microbiology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
Miyamoto
Michiko
M
Furusaka
Akihiro
A
Date
Tomoko
T
Yasui
Kotaro
K
Kato
Junko
J
Matsushima
Shozo
S
Komatsu
Tatsuji
T
Wakita
Takaji
T
D000328:Adult; D000595:Amino Acid Sequence; D002460:Cell Line; D005260:Female; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000821:virology; D006801:Humans; D017093:Liver Failure / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D016415:Sequence Alignment; D014162:Transfection; D014758:Viral Core Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D011498:Protein Precursors; D014758:Viral Core Proteins