NS5A phosphorylation: its functional role in the life cycle of hepatitis C virus

Abstract

ABSTRACT  Hepatitis C virus (HCV) is a major cause of liver disease. HCV RNA replicates in a membrane-associated replication complex. Nonstructural protein 5A (NS5A) is phosphorylated on multiple serine and threonine residues and exists in basally phosphorylated and hyperphosphorylated forms. To date, studies have identified several serine/threonine kinases responsible for NS5A phosphorylation. Although NS5A has no known enzymatic activity, it is a multifunctional protein required for HCV RNA replication and virion assembly. The phosphorylation status of NS5A is considered to have a significant impact on its function and the viral life cycle. Furthermore, NS5A inhibitors represent a new class of direct acting antivirals and have become a key component for effective combination therapies against HCV infection.