Comparative Studies of the Core Gene Products of Two Different Hepatitis C Virus Isolates: Two Alternative Forms Determined by a Single Amino Acid Substitution

Virology. 1994 Feb 15;199(1):124-31. doi: 10.1006/viro.1994.1104.

Abstract

We have compared the expression of the core gene of two different hepatitis C virus (HCV) isolates, HCV-1 and HCV-RH, using the in vitro translation assay. In the absence of the downstream E1 envelope protein sequence, a 16-kDa protein (P16) was the dominant protein product synthesized from the HCV-1 core gene sequence. On the other hand, a 21-kDa protein (P21) was the dominant protein product synthesized from the HCV-RH sequence. Domain-swapping and site-directed mutagenesis experiments indicated that codon 9 of the core protein coding sequence played a crucial role on the synthesis of the core protein: a lysine codon at this position led to the synthesis of P16 and an arginine codon at this position led to the synthesis of P21. For HCV-1 and HCV-RH, this codon encodes lysine and arginine, respectively. Further analyses indicated that P16 was likely co-amino-terminal with P21. In the presence of the downstream E1 envelope protein sequence and microsomal membranes, P16 as well as P21 were synthesized from the HCV-1 core gene sequence whereas P21 remained the only detectable protein product synthesized from the HCV-RH core gene sequence. These results indicate that the pathway leading to the synthesis of the HCV core protein may be more complicated than originally envisioned.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cloning, Molecular
  • DNA, Viral
  • Gene Expression
  • Genes, Viral
  • Hepacivirus / genetics*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Viral Core Proteins / genetics*

Substances

  • 16 kDa protein, hepatitis C virus
  • 21 kDa protein, hepatitis C virus
  • DNA, Viral
  • Viral Core Proteins