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J Gen Virol 85 (2004), 2299-2306; DOI 10.1099/vir.0.80028-0

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© 2004 Society for General Microbiology

Short Communication

Functional properties of a 16 kDa protein translated from an alternative open reading frame of the core-encoding genomic region of hepatitis C virus

Arnab Basu1, Robert Steele2, Ranjit Ray1,3 and Ratna B. Ray1,2

1 Department of Internal Medicine, Saint Louis University, St Louis, MO 63110, USA
2 Department of Pathology, Saint Louis University, St Louis, MO 63110, USA
3 Department of Molecular Microbiology and Immunology, Saint Louis University, St Louis, MO 63110, USA

Correspondence
Ranjit Ray
rayr{at}slu.edu

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.




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