Synthesis of a novel hepatitis C virus protein by ribosomal frameshift.
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.
Xu
Z
Z
Department of Molecular Microbiology and Immunology, University of Southern California, 2011 Zonal Avenue, HMR-401, Los Angeles, CA 90033, USA.
Choi
J
J
Yen
T S
TS
Lu
W
W
Strohecker
A
A
Govindarajan
S
S
Chien
D
D
Selby
M J
MJ
Ou
J
J
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*
D003062:Codon; D004279:DNA, Viral; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus