KDEL Receptors Assist Dengue Virus Exit from the Endoplasmic Reticulum
Ming Yuan Li,
Marc Grandadam,
Kevin Kwok,
Thibault Lagache,
Yu Lam Siu,
Jing Shu Zhang,
Kouxiong Sayteng,
Mateusz Kudelko,
Cheng Feng Qin,
Jean-Christophe Olivo-Marin,
Roberto Bruzzone,
Pei Gang Wang
Affiliations
Ming Yuan Li
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
Marc Grandadam
Institut Pasteur du Laos, Vientiane, Lao PDR
Kevin Kwok
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
Thibault Lagache
Unité d’Analyse d’Images Biologiques, CNRS URA 2582, Department of Cell Biology and Infection, Institut Pasteur, 75015 Paris Cedex, France
Yu Lam Siu
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
Jing Shu Zhang
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
Kouxiong Sayteng
Institut Pasteur du Laos, Vientiane, Lao PDR
Mateusz Kudelko
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
Cheng Feng Qin
Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China
Jean-Christophe Olivo-Marin
Unité d’Analyse d’Images Biologiques, CNRS URA 2582, Department of Cell Biology and Infection, Institut Pasteur, 75015 Paris Cedex, France
Roberto Bruzzone
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
Pei Gang Wang
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
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.
