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Published online ahead of print on 4 March 2009 as doi:10.1099/vir.0.007914-0
Journal of General Virology 2009;90:1093.

A more recent version of this article appeared on May 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.007914-0
© 2009 Society for General Microbiology
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A role for autophagolysosomes in DEN-3 production in HepG2 cells

Atefeh Khakpoor1, Mingkwan Panyasrivanit1, Nitwara Wikan1 and Duncan R. Smith2,3

1 Mahidol University;
2 Mahidol University, Thailand

3 E-mail: duncan_r_smith{at}hotmail.com

We have recently proposed that amphisomes act as a site for translation and replication of DEN-2, and proposed that DEN-2 entry and replication are linked through an ongoing association with membranes of an endosomal-autophagosomal lineage. In this report we present the results of an investigation into the interaction between DEN-3 and the autophagy machinery. Critically, treatment with the lysosomal fusion inhibitor L-asparagine discriminated the interaction of DEN-3 from that of DEN-2. Inhibition of fusion of autophagosomes and amphisomes with lysosomes resulted in a decreased DEN-3 production, implying a role for the autophagolysosome in the DEN-3 life cycle. Evidence based upon the co-localization of LC3 and cathepsin D with dsRNA and NS1 protein as assessed by confocal microscopy support a model in which DEN-3 interacts with both amphisomes and autophagolysosomes. These results demonstrate that the interaction between dengue virus and the host cell autophagy machinery are complex, and may in part be determined by viral encoded factors.

Received 14 October 2008; accepted 19 January 2009.




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