title: KDEL Receptors Assist Dengue Virus Exit from the Endoplasmic Reticulum.
abstract: Membrane receptors at the surface of target cells are key host factors for virion entry; however, it is unknown whether trafficking and secretion of progeny virus requires host intracellular receptors. In this study, we demonstrate that dengue virus (DENV) interacts with KDEL receptors (KDELR), which cycle between the ER and Golgi apparatus, for vesicular transport from ER to Golgi. Depletion of KDELR by siRNA reduced egress of both DENV progeny and recombinant subviral particles (RSPs). Coimmunoprecipitation of KDELR with dengue structural protein prM required three positively charged residues at the N terminus, whose mutation disrupted protein interaction and inhibited RSP transport from the ER to the Golgi. Finally, siRNA depletion of class II Arfs, which results in KDELR accumulation in the Golgi, phenocopied results obtained with mutagenized prME and KDELR knockdown. Our results have uncovered a function for KDELR as an internal receptor involved in DENV trafficking.
authors.affiliation: HKU-Pasteur Research Pole and Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Ming Yuan
authors.initials: MY
authors.lastname: Li
authors.affiliation: Institut Pasteur du Laos, Vientiane, Lao PDR.
authors.forename: Marc
authors.initials: M
authors.lastname: Grandadam
authors.affiliation: HKU-Pasteur Research Pole and Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kwok
authors.affiliation: Unité d'Analyse d'Images Biologiques, CNRS URA 2582, Department of Cell Biology and Infection, Institut Pasteur, 75015 Paris Cedex, France; Department of Cell Biology and Infection, Institut Pasteur, 75015 Paris Cedex, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Lagache
authors.affiliation: HKU-Pasteur Research Pole and Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yu Lam
authors.initials: YL
authors.lastname: Siu
authors.affiliation: HKU-Pasteur Research Pole and Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Jing Shu
authors.initials: JS
authors.lastname: Zhang
authors.affiliation: Institut Pasteur du Laos, Vientiane, Lao PDR.
authors.forename: Kouxiong
authors.initials: K
authors.lastname: Sayteng
authors.affiliation: HKU-Pasteur Research Pole and Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kudelko
authors.affiliation: Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.
authors.forename: Cheng Feng
authors.initials: CF
authors.lastname: Qin
authors.affiliation: Unité d'Analyse d'Images Biologiques, CNRS URA 2582, Department of Cell Biology and Infection, Institut Pasteur, 75015 Paris Cedex, France; Department of Cell Biology and Infection, Institut Pasteur, 75015 Paris Cedex, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Olivo-Marin
authors.affiliation: HKU-Pasteur Research Pole and Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Department of Cell Biology and Infection, Institut Pasteur, 75015 Paris Cedex, France. Electronic address: bruzzone@hku.hk.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bruzzone
authors.affiliation: HKU-Pasteur Research Pole and Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, PR China. Electronic address: pgwang@163.com.
authors.forename: Pei Gang
authors.initials: PG
authors.lastname: Wang