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Originally published as JGV in Press, 10.1099/vir.0.007914-0 on March 4, 2009 J Gen Virol 90 (2009), 1093-1103; DOI 10.1099/vir.0.007914-0

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A role for autophagolysosomes in dengue virus 3 production in HepG2 cells

Atefeh Khakpoor, Mingkwan Panyasrivanit, Nitwara Wikan and Duncan R. Smith

Molecular Pathology Laboratory, Institute of Molecular Biology and Genetics, Mahidol University, Thailand

Correspondence
Duncan R. Smith
duncan_r_smith{at}hotmail.com

We have recently proposed that amphisomes act as a site for translation and replication of dengue virus (DENV)-2 and that DENV-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 DENV-3 and the autophagy machinery. Critically, treatment with the lysosomal fusion inhibitor L-asparagine differentiated the interaction of DENV-3 from that of DENV-2. Inhibition of fusion of autophagosomes and amphisomes with lysosomes resulted in decreased DENV-3 production, implying a role for the autophagolysosome in the DENV-3 life cycle. Evidence based upon the co-localization of LC3 and cathepsin D with double stranded RNA and NS1 protein, as assessed by confocal microscopy, support a model in which DENV-3 interacts with both amphisomes and autophagolysosomes. These results demonstrate that the interactions between DENV and the host cell autophagy machinery are complex and may be determined in part by virus-encoded factors.






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