Dissecting the Roles of the 5′ Exoribonucleases Xrn1 and Xrn2 in Restricting Hepatitis C Virus Replication

Abstract

HCV is a common cause of liver disease both within and outside the United States. Its replication is dependent upon a small, liver-specific noncoding RNA, miR-122. Although this requirement has been exploited for the development of an anti-miR-122 antagomir as a host-targeting antiviral, the molecular mechanisms underpinning the host factor activity of miR-122 remain incompletely defined. Conflicting reports suggest miR-122 protects the viral RNA against decay mediated by distinct cellular 5' exoribonucleases, Xrn1 and Xrn2. Here, we compare the roles of these two exoribonucleases in HCV-infected cells and confirm that Xrn1, not Xrn2, is primarily responsible for decay of RNA in cells infected with multiple virus strains. Our results clarify previously published research and add to the current understanding of the host factor requirement for miR-122.