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

Journal of General Virology - Tập 90 Số 5 - Trang 1093-1103 - 2009
Atefeh Khakpoor1, Mingkwan Greenwood1, Nitwara Wikan1, Stan B. Sidhu1
1Molecular Pathology Laboratory, Institute of Molecular Biology and Genetics, Mahidol University, Thailand

Tóm tắt

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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Journal of General Virology

Tập 90 Số 5

1093-1103

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