The ubiquitin-proteasome system facilitates the transfer of murine coronavirus from endosome to cytoplasm during virus entry

The ubiquitin-proteasome system is involved in cellular endocytosis and maturation of some viruses. In this study, we found that proteasome inhibitors blocked mouse hepatitis virus replication at an early step in the viral life cycle. In the presence of MG132, the entering viruses accumulated in both the endosome and denser lysosome, suggesting that the ubiquitin-proteasome system is involved in the release of virus from the endosome to the cytosol during the virus entry step. Mouse hepatitis virus (MHV) is an enveloped virus with a positive-stranded, nonsegmented RNA genome of about 32 kb (12). MHV belongs to the Coronaviridae family, which includes the recently emerged virus, severe acute respiratory syndrome (SARS) coronavirus (7). Since the ubiquitin-proteasome sys-tem is a fundamental machinery in the cell (9, 11, 14, 19) and has been shown to be involved in the replication, particularly virion maturation, of several viruses (4, 5, 8, 16–18), we are interested in knowing whether the ubiquitin-proteasome sys-tem is also involved in MHV replication