DECIPHERING THE HOST-PATHOGEN INTERACTIONS DURING ENTEROVIRUS-A71 INFECTION IN MOTOR NEURON CELLS: ROLE OF PERIPHERIN AND ITS INTERACTING PARTNERS

Abstract

Cyclical epidemics of Enterovirus A71 (EV-A71) infections, responsible for Hand, Foot and Mouth Disease (HFMD), have raised serious public health concern in the Asia-Pacific region due to propensity of this virus to cause neurological complications. Here, I examined the role of PRPH, a type III intermediate neurofilament, during EV-A71 infection, and investigated the interactions between PRPH and viral components. Surface-expressed PRPH facilitated viral entry, while intracellular PRPH influenced viral genome replication through interactions with structural and non-structural viral components. Importantly, PRPH was not involved 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 invasion of the central nervous system. Finally, I showed that EV-A71 exploited some of the PRPH interacting partners. Of which, small GTP binding protein Rac1 was identified as a promising druggable host target to limit EV-A71 neuroinvasion.