title: Co-localization of constituents of the dengue virus translation and replication machinery with amphisomes.
abstract: 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.
authors.affiliation: Molecular Pathology Laboratory, Institute of Molecular Biology and Genetics, Mahidol University, Thailand.
authors.forename: Mingkwan
authors.initials: M
authors.lastname: Panyasrivanit
authors.affiliation: Molecular Pathology Laboratory, Institute of Molecular Biology and Genetics, Mahidol University, Thailand.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Khakpoor
authors.affiliation: Molecular Pathology Laboratory, Institute of Molecular Biology and Genetics, Mahidol University, Thailand.
authors.forename: Nitwara
authors.initials: N
authors.lastname: Wikan
authors.affiliation: Molecular Pathology Laboratory, Institute of Molecular Biology and Genetics, Mahidol University, Thailand.
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Smith
mesh_terms: D000330:Aedes / Q000821:virology; D000818:Animals; D001343:Autophagy; D001733:Bites and Stings / Q000821:virology; D006528:Carcinoma, Hepatocellular / Q000821:virology; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops / Q000821:virology; D003715:Dengue / Q000453:epidemiology / Q000635:transmission; D003716:Dengue Virus / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology; D018613:Microscopy, Confocal; D014176:Protein Biosynthesis; D014779:Virus Replication / Q000502:physiology*