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.

EMBO Reports
|April 19, 2021
PubMed

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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