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Updated: Nov 8, 2025

Viral Tracing of Genetically Defined Neural Circuitry
Published on: October 17, 2012
Enterovirus-A71 exploits peripherin and Rac1 to invade the central nervous system
Ze Qin Lim1,2, Qing Yong Ng1,2, Yukei Oo1,2
1Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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.
Insights
Enterovirus-A71 (EV-A71) uses peripherin (PRPH) to invade the central nervous system, unlike other hand, foot, and mouth disease viruses. Targeting PRPH interactions, like with Rac1, may block EV-A71 neuroinvasion.
Area of Science:
- Neurovirology
- Molecular Neuroscience
- Infectious Diseases
Background:
- Enterovirus-A71 (EV-A71) causes severe neurological hand, foot, and mouth disease (HFMD).
- EV-A71 invades the central nervous system (CNS) via motor neuron infection at neuromuscular junctions (NMJs).
- Peripherin (PRPH), a type III intermediate neurofilament, is implicated in neurodegenerative disorders.
Purpose of the Study:
- To investigate the role of peripherin (PRPH) in EV-A71 infection and neuroinvasion.
- To determine if PRPH is a unique factor exploited by EV-A71 for CNS entry.
- To identify potential host targets for limiting EV-A71 neuroinvasion.
Main Methods:
- Co-localization studies of PRPH and EV-A71 in infected mice (NMJs, spinal cord).
- Cell-based assays using motor neuron and neuroblastoma cell lines to assess PRPH's role in viral entry and replication.
- Comparative infection studies with coxsackievirus A16.
- Identification and analysis of PRPH-interacting viral and host factors.
Main Results:
- PRPH co-localizes with EV-A71 in mouse NMJs and spinal cord.
- Surface PRPH facilitates EV-A71 entry; intracellular PRPH aids viral genome replication.
- PRPH is not essential for coxsackievirus A16 infection, highlighting EV-A71's specific exploitation.
- EV-A71 interacts with PRPH partners, including Rac1, a potential druggable target.
Conclusions:
- Peripherin is a key host factor exploited by EV-A71 for neuroinvasion.
- EV-A71's unique ability to utilize PRPH contributes to its neurological pathogenicity.
- Targeting PRPH-interacting proteins, such as Rac1, offers a potential therapeutic strategy against EV-A71 neuroinvasion.
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