Synthesis of a novel hepatitis C virus protein by ribosomal frameshift

Zhenming Xu, Jinah Choi, T. S.Benedict Yen, Wen Lu, Anne Strohecker, Sugantha Govindarajan, David Chien, Mark J. Selby, Jing Hsiung Ou

Research output: Contribution to journalArticlepeer-review

246 Scopus citations

Abstract

Hepatitis C virus (HCV) is an important human pathogen that affects ∼100 million people worldwide. Its RNA genome codes for a polyprotein, which is cleaved by viral and cellular proteases to produce at least 10 mature viral protein products. We report here the discovery of a novel HCV protein synthesized by ribosomal frameshift. This protein, which we named the F protein, is synthesized from the initiation codon of the polyprotein sequence followed by ribosomal frameshift into the -2/+1 reading frame. This ribosomal frameshift requires only codons 8-14 of the core protein-coding sequence, and the shift junction is located at or near codon 11. An F protein analog synthesized in vitro reacted with the sera of HCV patients but not with the sera of hepatitis B patients, indicating the expression of the F protein during natural HCV infection. This unexpected finding may open new avenues for the development of anti-HCV drugs.

Original languageEnglish (US)
Pages (from-to)3840-3848
Number of pages9
JournalEMBO Journal
Volume20
Issue number14
DOIs
StatePublished - Jul 16 2001
Externally publishedYes

Keywords

  • HCV F protein
  • HCV core protein
  • Hepatitis C virus
  • Ribosomal frameshift

ASJC Scopus subject areas

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • Molecular Biology
  • General Neuroscience

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