Role of E2/E3 ubiquitin ligase, UBE2O, in Hepatitis B virus replication

Abstract

Chronic hepatitis represents a life-long liver disease caused by infection of Hepatitis B virus (HBV) and affecting more than 250 million people worldwide. Since HBV replication is completely dependent upon host cell protein pathways, the study of virus-host interactions promises to reveal novel cellular targets for development of new therapies. Our strategy is to identify and characterize key cellular proteins and pathways that are essential for different steps of viral replication1,2. Using mass spectrometry, we identified a novel HBV Core (HBc) - interacting host protein, UBE2O3. UBE2O is an E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates mono-ubiquitination of several chromatin-associated proteins, such as INO80, BAP1 and CXXC1, affecting their subcellular location4. Notably, UBE2O is also implicated in endosomal protein trafficking through its ubiquitination of the WASH regulatory complex5.