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Title: Enterovirus-A71 exploits peripherin and Rac1 to invade the central nervous system
Authors: Lim, Ze Qin
Ng, Qing Yong
Oo, Yukei 
Chu, Justin Jang Hann 
Ng, Shi Yan
Sze, Siu Kwan 
Alonso, Sylvie 
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
and mouth disease
Rac 1
Issue Date: 19-Apr-2021
Publisher: WILEY
Citation: Lim, Ze Qin, Ng, Qing Yong, Oo, Yukei, Chu, Justin Jang Hann, Ng, Shi Yan, Sze, Siu Kwan, Alonso, Sylvie (2021-04-19). Enterovirus-A71 exploits peripherin and Rac1 to invade the central nervous system. EMBO REPORTS 22 (6). ScholarBank@NUS Repository.
Abstract: Enterovirus-A71 (EV-A71) has been associated with severe neurological forms of hand, foot, and mouth disease (HFMD). EV-A71 infects motor neurons at neuromuscular junctions (NMJs) to invade the central nervous system (CNS). Here, we investigate the role of peripherin (PRPH) during EV-A71 infection, a type III intermediate neurofilament involved in neurodegenerative conditions. In mice infected with EV-A71, PRPH co-localizes with viral particles in the muscles at NMJs and in the spinal cord. In motor neuron-like and neuroblastoma cell lines, surface-expressed PRPH facilitates viral entry, while intracellular PRPH influences viral genome replication through interactions with structural and non-structural viral components. Importantly, PRPH does not play a role during infection with coxsackievirus A16, another causative agent of HFMD rarely associated with neurological complications, suggesting that EV-A71 ability to exploit PRPH represents a unique attribute for successful CNS invasion. Finally, we show that EV-A71 also exploits some of the many PRPH-interacting partners. Of these, small GTP-binding protein Rac1 represents a potential druggable host target to limit neuroinvasion of EV-A71.
Source Title: EMBO REPORTS
ISSN: 1469-221X
DOI: 10.15252/embr.202051777
Appears in Collections:Staff Publications

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