Summary auto-generated
This study investigated the functional properties of a 16 kDa hepatitis C virus (HCV) protein (designated F/ARFP/core+1 ORF) translated from an alternative reading frame of the HCV core genomic region. The researchers compared the F protein's functions with those of the canonical HCV core protein, which is known to modulate cellular gene expression, inhibit apoptosis, and promote cell growth. Using HepG2 cells and rat embryo fibroblasts, they examined effects on transcription of cellular promoters (c-myc, hTERT, p53, p21), TNF-alpha-induced apoptosis, and cell growth. Results showed that the F protein did not significantly activate c-myc or hTERT promoters and did not suppress p53 promoter activity, unlike the core protein. However, both proteins repressed p21 expression. The F protein failed to inhibit TNF-alpha-mediated apoptosis or promote fibroblast growth, distinguishing it functionally from the core protein. In conclusion, the F protein does not share major functional properties of the HCV core protein except for p21 repression, suggesting it may have distinct roles in HCV pathogenesis.
Key findings
- The F protein does not significantly modulate c-myc, hTERT, or p53 promoter activities, unlike the HCV core protein
- Both F and core proteins repress p21 gene expression, though the core protein is more potent
- The F protein does not protect against TNF-alpha-mediated apoptosis in HepG2 cells, contrasting with the protective effect of core protein
- The F protein does not promote cell growth in rat embryo fibroblasts, unlike the core protein which showed at least twofold higher growth rates
- The F protein and core protein have mostly distinct functional properties despite being encoded from the same genomic region
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Abstract
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 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.