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Journal of Virology, September 2008, p. 9143-9153, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00641-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Autophagosome Supports Coxsackievirus B3 Replication in Host Cells{triangledown}

Jerry Wong, Jingchun Zhang, Xiaoning Si, Guang Gao, Ivy Mao, Bruce M. McManus, and Honglin Luo*

The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Providence Heart + Lung Institute, St. Paul's Hospital, Vancouver, British Columbia, Canada

Received 21 March 2008/ Accepted 27 June 2008

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.

* Corresponding author. Mailing address: The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia-St. Paul's Hospital, 1081 Burrard St., Vancouver, British Columbia, Canada V6Z 1Y6. Phone: (604) 682-2344, ext. 62847. Fax: (604) 806-9274. E-mail: hluo{at}mrl.ubc.ca

{triangledown} Published ahead of print on 2 July 2008.

Journal of Virology, September 2008, p. 9143-9153, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00641-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wang, Y., Weiss, L. M., Orlofsky, A. (2009). Host Cell Autophagy Is Induced by Toxoplasma gondii and Contributes to Parasite Growth. J. Biol. Chem. 284: 1694-1701 [Abstract] [Full Text]  


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