ROLE OF HUMAN UBIQUITIN LIGASES IN ENTEROVIRUS- 71 HUMAN HOST CELL INTERACTIONS

Abstract

Enterovirus 71is an emerging RNA virus causing major human health problems such as hand-foot-and-mouth disease as well as neurological complications. It is believed that host factors play a role in the EV71 pathogenesis but little is known about their identity or underlying mechanisms. Although ubiquitination is critical for regulating key cellular processes and immune responses, the ?global role of ubiquitination processes? in EV71infection of human host cells is not yet determined. To address this, we over-expressed >90% of E3 Ubiquitin ligases [UBL] and their adaptors in HEK 293T cells, assessed their ability to modulate EV71 infection by immunofluorescence staining coupled with high-content microscopy and statistical data analysis. We identified 54 pro-viral and 65 antiviral UBLs. Counter screen of these hit UBLs with dengue virus revealed both panviral and virus-specific effect of UBLs. Subsequent mechanistic studies indicated that a subset of 10 antiviral UBLs potentially inhibited EV71 by degrading SCARB2 receptor.