RNA viruses are a major health problem of humans and domesticated animals globally. The RNA virus-host cell co-evolution has led to both the pathogens and the hosts adapting to control each other. Yet, the mechanisms by which host cells resist RNA viral infection is incompletely understood. The ubiquitin ligases are a family of human proteins involved in both the regulation of cellular signaling and functioning of proteins. Given their importance in cell physiology, it is likely that ubiquitin ligases may have a prominent role in either supporting (proviral factor) or restricting (restriction factor) viral infection. However, till date, no study has evaluated the role of ubiquitin ligases in the infection of RNA viruses at a genome scale, and thus there is a paucity of information on their role in host-virus interactions.
EV71 is an RNA virus causing major human health problems such as handfoot- and-mouth disease as well as neurological complications. Although ubiquitination is critical for regulating key cellular processes and immune responses, the “global role of ubiquitination processes” in ENTEROVIRUS 71 infection of human host cells is not determined till date. To address this, we systematically over expressed >90% of the ubuquitination-mediating genes (E3 Ubiquitin ligases [UBL] and their adaptors) encoded in human-genome in 293T cells, infected the cells with ENTEROVIRUS 71 for 24h, and determined viral load using immune-fluorescence staining coupled with highcontent 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 pan-viral and virus-specific effect of UBLS on infection. Subsequent mechanistic studies indicated that a subset of 10 antiviral UBLs potentially inhibited EV71 by degrading its receptors SCARB2. Our study thus identified several novel UBLs impacting on EV71 infection, revealing novel aspects of EV71-host cell interactions.
|School:||National University of Singapore (Singapore)|
|School Location:||Republic of Singapore|
|Source:||MAI 55/03M(E), Masters Abstracts International|
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