The major form of hepatitis C virus alternate reading frame protein is suppressed by core protein expression.

Nucleic Acids Research
Marie WolfCatherine Schuster

Abstract

Hepatitis C virus (HCV) is a human RNA virus encoding 10 proteins in a single open reading frame. In the +1 frame, an 'alternate reading frame' (ARF) overlaps with the core protein-encoding sequence and encodes the ARF protein (ARFP). Here, we investigated the molecular regulatory mechanisms of ARFP expression in HCV target cells. Chimeric HCV-luciferase reporter constructs derived from the infectious HCV prototype isolate H77 were transfected into hepatocyte-derived cell lines. Translation initiation was most efficient at the internal AUG codon at position 86/88, resulting in the synthesis of a truncated ARFP named (86/88)ARFP. Interestingly, (86/88)ARFP synthesis was markedly enhanced in constructs containing an inactivated core protein reading frame. This enhancement was reversed by co-expression of core protein in trans, demonstrating suppression of ARFP synthesis by HCV core protein. In conclusion, our results indicate that translation of ARFP occurs mainly by alternative internal initiation at position 86/88 and is regulated by HCV core protein expression. The suppression of ARFP translation by HCV core protein suggests that ARFP expression is inversely linked to the level of viral replication. These findings define key m...Continue Reading

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Citations

Feb 15, 2011·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·H QureshiS A Qureshi
May 1, 2013·Biochemical and Biophysical Research Communications·Wen-Ta HuShih-Yen Lo
Dec 4, 2009·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Christian DrouinNaglaa H Shoukry
Jan 14, 2010·The FEBS Journal·Anissa BoumlicGeorges Orfanoudakis
Dec 17, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Wagane J A BengaCatherine Schuster
Nov 25, 2014·Cell·Karim MajzoubJean-Luc Imler
Apr 2, 2020·International Journal of Molecular Sciences·Michael Niepmann, Gesche K Gerresheim
May 30, 2020·Journal of Medical Virology·Mahdi MohamadiMehdi Ajorloo

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Methods Mentioned

BETA
PCR
transfection
transfections

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