Journal
FUTURE MICROBIOLOGY
Volume 11, Issue 10, Pages 1227-1248Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/fmb-2016-0002
Keywords
actin regulation; Caveolin-1; EGFR; endocytosis; Japanese encephalitis virus; neuronal cells
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Funding
- National Natural Science Foundation of China [31370196, 81221061, 81273557, 81302812]
- Military ST Project [AWS11C001]
- Medical Youth Science Program [13QNP100]
- Shanghai Municipal Natural Science Foundation [13ZR1449300]
- National S&T Major Project for Infectious Diseases Control [2013ZX10004104]
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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.
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