Autophagosome supports coxsackievirus B3 replication in host cells.

TitleAutophagosome supports coxsackievirus B3 replication in host cells.
Publication TypeJournal Article
Year of Publication2008
AuthorsWong, J, Zhang, J, Si, X, Gao, G, Mao, I, McManus, BM, Luo, H
JournalJournal of Virology
Date Published2008 Sep
KeywordsAdenine, Apoptosis Regulatory Proteins, Autophagy, Cell Line, Enterovirus B, Human, HeLa Cells, Humans, Lysosomes, Membrane Proteins, Phagosomes, RNA, Small Interfering, Ubiquitin-Activating Enzymes, Virus Replication

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.

Alternate JournalJ. Virol.
PubMed ID18596087
PubMed Central IDPMC2546883
Grant List79921-1 / / Canadian Institutes of Health Research / Canada
92214-1 / / Canadian Institutes of Health Research / Canada
97749-1 / / Canadian Institutes of Health Research / Canada