Journal
EMBO REPORTS
Volume 22, Issue 6, Pages -Publisher
WILEY
DOI: 10.15252/embr.202051777
Keywords
Enterovirus‐ A71; hand; foot; and mouth disease; neurotropism; peripherin; Rac 1
Categories
Funding
- National Medical Research Council [NMRC/ CBRG/0098/2015]
- National Research Foundation [CRP21-2018-0101]
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PRPH plays a crucial role in EV-A71 infection by facilitating viral entry and influencing viral genome replication. The ability of EV-A71 to exploit PRPH for successful invasion of the central nervous system represents a unique attribute, with small GTP-binding protein Rac1 potentially serving as a druggable host target to limit neuroinvasion.
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.
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