Functional properties of a 16 kDa protein translated from an alternative open reading frame of the core-encoding genomic region of hepatitis C virus.
Hepatitis C virus (HCV) often causes persistent infection in humans. This could be due in part to the effect of viral proteins on cellular gene expression. Earlier observations suggest that the HCV core protein expressed from genotype 1a modulates important cellular genes at the transcriptional level, affects programmed cell death (apoptosis) and promotes cell growth. Recently, different groups of investigators have reported the translation of an approximately 16 kDa protein (named F/ARFP/core+1 ORF) from an alternate open reading frame of the HCV core-encoding genomic region. The functional significance of this F protein is presently unknown. Thus, whether the F and core proteins have both shared and distinct functions was investigated here. The experimental observations suggested that the F protein does not significantly modulate c-myc, hTERT and p53 promoter activities, unlike the HCV core protein. Interestingly, the F protein repressed p21 expression. Further studies indicated that the F protein does not inhibit tumour necrosis factor alpha-mediated apoptosis of HepG2 cells or promote rat embryo fibroblast growth. Taken together, these results suggest that the F protein does not share major properties identified previously for the HCV core protein, other than regulating p21 expression.
Department of Internal Medicine, Saint Louis University, St Louis, MO 63110, USA.
Arnab
A
Basu
Department of Pathology, Saint Louis University, St Louis, MO 63110, USA.
Robert
R
Steele
Department of Molecular Microbiology and Immunology, Saint Louis University, St Louis, MO 63110, USA.|Department of Internal Medicine, Saint Louis University, St Louis, MO 63110, USA.
Ranjit
R
Ray
Department of Pathology, Saint Louis University, St Louis, MO 63110, USA.|Department of Internal Medicine, Saint Louis University, St Louis, MO 63110, USA.
Ratna B
RB
Ray
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004268:DNA-Binding Proteins; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics*; D008970:Molecular Weight; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D019098:Telomerase / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics*; D014760:Viral Fusion Proteins / Q000502:physiology*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D014758:Viral Core Proteins; D014760:Viral Fusion Proteins; D019098:Telomerase