Biomaterial Database

KDEL Receptors Assist Dengue Virus Exit from the Endoplasmic Reticulum. 2015

Ming Yuan Li, and Marc Grandadam, and Kevin Kwok, and Thibault Lagache, and Yu Lam Siu, and Jing Shu Zhang, and Kouxiong Sayteng, and Mateusz Kudelko, and Cheng Feng Qin, and Jean-Christophe Olivo-Marin, and Roberto Bruzzone, and 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.