Studies on the interaction of hepatitis C virus NS4A protein with cellular proteins

Abstract

The genomic RNA of Hepatitis C virus (HCV) contains a single large open reading frame for virion structural and nonstructural polypeptides. This polyprotein of about 3,000 amino acids is cleaved to 9 proteins by cellular and viral proteases. Among these proteins, NS4A is associated with NS5A phosphorylation and stabilizes viral protease NS3, so assists in its localization in the endoplasmic reticulum (ER) membrane. But there is little knowledge about the cellular factors that can interact with NS4A. These experiments were done with the purpose of understading the more detailed function of NS4A by finding the cellular protein expressed in mouse liver cDNA library through yeast two-hybrid method. As a result, it was revealed that mouse $α_1$-antitrypsin bound NS4A. $α_1$-antitrypsin is a member of the serine protease inhibitor present mainly in the cytoplasm. considering that the viral protease NS3 is also a serine protease, NS3 can be a substrate for $α_1$-antitrypsin and we can infer that the unknown function of NS4A is to protect NS3 by interaction with $α_1$-antitrypsin. But to prove this hypothesis, the experiments which show that $α_1$-antitrypsin can inhibit HCV NS3 should be preceded.