Since the first discovery that human papillomavirus protein E6 targets the cellular tumor suppressor protein p53 for the UPSmediated degradation [16] , increasing studies, including those from our laboratory, have suggested that various viruses evolve different mechanisms to utilize or manipulate the host UPS for their own benefits [9, [20] [21] [22] [23] [24] [25] . We have previously shown that CVB3 infection results in downregulation of several host proteins [7, 9] , such as cell-cycle protein cyclin D1, tumor suppressor p53, and transcription activator b-catenin in infected HeLa cells. The downregulation of host proteins following CVB3 infection is most likely through the UPS. Specific inhibitors to 26S proteasome reverse the degradation of proteins in HeLa cells [7, 9] and reduce CVB3 replication in murine cardiomyocytes [26] .