Oncotarget

Research Papers:

Newcastle disease virus employs macropinocytosis and Rab5a-dependent intracellular trafficking to infect DF-1 cells

Lei Tan, Yuqiang Zhang, Yuan Zhan, Yanmei Yuan, Yingjie Sun, Xusheng Qiu, Chunchun Meng, Cuiping Song, Ying Liao and Chan Ding _

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Oncotarget. 2016; 7:86117-86133. https://doi.org/10.18632/oncotarget.13345

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Abstract

Lei Tan1,*, Yuqiang Zhang1,*, Yuan Zhan1, Yanmei Yuan1, Yingjie Sun1, Xusheng Qiu1, Chunchun Meng1, Cuiping Song1, Ying Liao1, Chan Ding1,2

1Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, P.R. China

2Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, P.R. China

*These authors contributed equally to this work

Correspondence to:

Chan Ding, email: [email protected]

Keywords: newcastle disease virus, endocytosis, clathrin, macropinocytosis, Rab5a

Received: September 12, 2016     Accepted: November 08, 2016     Published: November 15, 2016

ABSTRACT

Oncolytic Newcastle disease virus (NDV) reportedly employs direct fusion of the viral envelope with the plasma membrane and caveolae-dependent endocytosis to enter cells. Here, we show that macropinocytosis and clathrin-mediated endocytosis are involved in NDV entry into a galline embryonic fibroblast cell line. Upon specific inhibition of clathrin assembly, GTPase dynamin, Na+/H+ exchangers, Ras-related C3 botulinum toxin substrate 1, p21 activated kinase 1 or protein kinase C, entry of NDV and its propagation were suppressed. NDV entry into cells triggers Rac1-Pak1 signaling and elicits actin rearrangement and plasma membrane ruffling. Moreover, NDV internalization within macropinosomes and trafficking involve Rab5a-positive vesicles. This is the first report demonstrating that NDV utilizes clathrin-mediated endocytosis and macropinocytosis as alternative endocytic pathways to enter cells. These findings shed new light on the molecular mechanisms underlying NDV entry into cells, and provide potential targets for NDV-mediated therapy in cancer.


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