title: Synthesis of a novel hepatitis C virus protein by ribosomal frameshift.
abstract: Hepatitis C virus (HCV) is an important human pathogen that affects approximately 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Southern California, 2011 Zonal Avenue, HMR-401, Los Angeles, CA 90033, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Choi
authors.forename: T S
authors.initials: TS
authors.lastname: Yen
authors.forename: W
authors.initials: W
authors.lastname: Lu
authors.forename: A
authors.initials: A
authors.lastname: Strohecker
authors.forename: S
authors.initials: S
authors.lastname: Govindarajan
authors.forename: D
authors.initials: D
authors.lastname: Chien
authors.forename: M J
authors.initials: MJ
authors.lastname: Selby
authors.forename: J
authors.initials: J
authors.lastname: Ou
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon; D004279:DNA, Viral; D018965:Frameshifting, Ribosomal; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D003062:Codon; D004279:DNA, Viral; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus