KDEL Receptors Assist Dengue Virus Exit from the Endoplasmic Reticulum

分类： 生物学 >> 生物物理学 >> 细胞生物学 提交时间： 2016-05-11

Li, Ming Yuan Kwok, Kevin Siu, Yu Lam Zhang, Jing Shu Kudelko, Mateusz Bruzzone, Roberto Wang, Pei Gang Li, Ming Yuan Kwok, Kevin Siu, Yu Lam Zhang, Jing Shu Kudelko, Mateusz Bruzzone, Roberto Wang, Pei Gang Grandadam, Marc Sayteng, Kouxiong Lagache, Thibault Olivo-Marin, Jean-Christophe Lagache, Thibault Olivo-Marin, Jean-Christophe

摘要： 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.

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