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J Gen Virol 90 (2009), 448-456; DOI 10.1099/vir.0.005355-0

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Co-localization of constituents of the dengue virus translation and replication machinery with amphisomes

Mingkwan Panyasrivanit, Atefeh Khakpoor, 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

Infections with dengue virus (DENV) are a significant public health concern in tropical and subtropical regions. However, little detail is known about how DENV interacts with the host-cell machinery to facilitate its translation and replication. In DENV-infected HepG2 cells, an increase in the level of LC3-II (microtubule-associated protein 1 light chain 3 form II), the autophagosomal membrane-bound form of LC3, was observed, and LC3 was found to co-localize with dsRNA and DENV NS1 protein, as well as ribosomal protein L28, indicating the presence of at least some of the DENV translation/replication machinery on autophagic vacuoles. Inhibition of fusion of autophagic vacuoles with lysosomes resulted in an increase in both intracellular and extracellular virus, and co-localization observed between mannose-6-phosphate receptor (MPR) and dsRNA and between MPR and LC3 identified the autophagic vacuoles as amphisomes. Amphisomes are formed as a result of fusion between endosomal and autophagic vacuoles, and as such provide a direct link between virus entry and subsequent replication and translation.




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A. Khakpoor, M. Panyasrivanit, N. Wikan, and D. R. Smith
A role for autophagolysosomes in dengue virus 3 production in HepG2 cells
J. Gen. Virol., May 1, 2009; 90(5): 1093 - 1103.
[Abstract] [Full Text] [PDF]




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