Recent studies suggest a possible takeover of host antimicrobial autophagy machinery by positive-stranded RNA viruses to facilitate their own replication. In the present study, we investigated the role of autophagy in coxsackievirus replication. Coxsackievirus B3 (CVB3), a picornavirus associated with viral myocarditis, causes pronounced intracellular membrane reorganization after infection. We demonstrate that CVB3 infection induces an increased number of double-membrane vesicles, accompanied by an increase of the LC3-II/LC3-I ratio and an accumulation of punctate GFP-LC3-expressing cells, two hallmarks of cellular autophagosome formation. However, protein expression analysis of p62, a marker for autophagy-mediated protein degradation, showed no apparent changes after CVB3 infection. These results suggest that CVB3 infection triggers autophagosome formation without promoting protein degradation by the lysosome. We further examined the role of the autophagosome in CVB3 replication. We demonstrated that inhibition of autophagosome formation by 3-methyladenine or small interfering RNAs targeting the genes critical for autophagosome formation (ATG7, Beclin-1, and VPS34 genes) significantly reduced viral replication. Conversely, induction of autophagy by rapamycin or nutrient deprivation resulted in increased viral replication. Finally, we examined the role of autophagosome-lysosome fusion in viral replication. We showed that blockage of the fusion by gene silencing of the lysosomal protein LAMP2 significantly promoted viral replication. Taken together, our results suggest that the host's autophagy machinery is activated during CVB3 infection to enhance the efficiency of viral replication.

REGgamma, a member of the 11S proteasome activators, has been shown to bind and activate the 20S proteasome to promote proteasome-dependent degradation of important regulatory proteins, such as SRC-3 and cyclin-dependent kinase inhibitors p21, p16, and p19, in a ubiquitin- and ATP-independent manner. Furthermore, REGgamma has been shown to facilitate the turnover of tumor suppressor p53 by promoting MDM2-mediated p53 ubiquitination. The discovery that REGgamma regulates cell-cycle regulators is consistent with previous studies where REGgamma-deficient mice have shown retardation in body growth, decreased cell proliferation and increased apoptosis, indicating a potential role of REGgamma in cancer development. Additionally, REGgamma's ability to promote viral protein degradation suggests its involvement in viral pathogenesis. This review presents an overview of the function of REGgamma, a summary of the current literature, and insight into the possible biological function of REGgamma relating to cancer, viral pathogenesis, and other diseases.