Qingqiang Xu1, Mingmei Cao2, Hongyuan Song3, Shenglin Chen1, Xijing Qian1, Ping Zhao1, Hao Ren1, Hailin Tang1, Yan Wang1, Youheng Wei4, Yongzhe Zhu1, Zhongtian Qi1. 1. Department of Microbiology, Second Military Medical University, Shanghai Key Laboratory of Medical Biodefense, Shanghai 200433, China. 2. Department of Medical Microbiology & Parasitology, Second Military Medical University, Shanghai 200433, China. 3. Department of Ophthalmology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. 4. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, China.
Abstract
AIM: To investigate the detailed mechanism of Japanese encephalitis virus (JEV) cell entry. MATERIALS & METHODS: Utilize a siRNA library targeting cellular membrane trafficking genes to identify key molecules that mediate JEV entry into human neuronal cells. RESULTS: JEV enters human neuronal cells by caveolin-1-mediated endocytosis, which depends on a two-step regulation of actin cytoskeleton remodeling triggered by RhoA and Rac1: RhoA activation promoted the phosphorylation of caveolin-1, and then Rac1 activation facilitated caveolin-associated viral internalization. Specifically, virus attachment activates the EGFR-PI3K signaling pathway, thereby leading to RhoA activation. CONCLUSION: This work provides a detailed picture of the entry route and intricate cellular events following the entry of JEV into human neuronal cells, and promotes a better understanding of JEV entry.
AIM: To investigate the detailed mechanism of Japanese encephalitis virus (JEV) cell entry. MATERIALS & METHODS: Utilize a siRNA library targeting cellular membrane trafficking genes to identify key molecules that mediate JEV entry into human neuronal cells. RESULTS:JEV enters human neuronal cells by caveolin-1-mediated endocytosis, which depends on a two-step regulation of actin cytoskeleton remodeling triggered by RhoA and Rac1: RhoA activation promoted the phosphorylation of caveolin-1, and then Rac1 activation facilitated caveolin-associated viral internalization. Specifically, virus attachment activates the EGFR-PI3K signaling pathway, thereby leading to RhoA activation. CONCLUSION: This work provides a detailed picture of the entry route and intricate cellular events following the entry of JEV into human neuronal cells, and promotes a better understanding of JEV entry.
Authors: Artur Szczepanski; Katarzyna Owczarek; Aleksandra Milewska; Zbigniew Baster; Zenon Rajfur; Judy A Mitchell; Krzysztof Pyrc Journal: Vet Res Date: 2018-07-03 Impact factor: 3.683
Authors: Katarzyna Owczarek; Artur Szczepanski; Aleksandra Milewska; Zbigniew Baster; Zenon Rajfur; Michal Sarna; Krzysztof Pyrc Journal: Sci Rep Date: 2018-05-08 Impact factor: 4.379