ROLE OF RAB11 IN ENTEROVIRUS 71 INFECTION CYCLE

Abstract

Enterovirus A71 (EV-A71) is a major causative agent of Hand, Foot and Mouth Disease (HFMD) and is associated with severe neurological complications. A siRNA screen using murine motor neuron-like NSC34 cells, identified Rab11a as a pro-viral host factor during EV-A71 infection. While validation using deconvoluted siRNA confirmed Rab11a's pro-viral nature in NSC34 cells, co-knockdown of Rab11a and Rab11b isoforms in neuroblastoma SH-SY5Y and rhabdomyosarcoma RD cell lines was required to impact EV-A71 infection, suggesting interchangeability of both isoforms. Rab11's role in infection is highly conserved across enteroviruses and different EV-A71 subgenotypes and CVA16. I demonstrated that Rab11 does not play a role in viral RNA synthesis, viral entry/uncoating, or IRES-dependent translation. Also, unlike previous studies, I found that Rab11’s vesicle trafficking function is dispensable during EV-A71 infection. Instead, my work supports that Rab11 acts as an adapter protein at the replication organelles, facilitating EV-A71 assembly/maturation by recruiting chaperones/chaperonins.