Identification Of Host Dependency Factors For Mers-cov Infection By Genome-wide Crispr-cas9 Screen

Abstract

Human infection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was first reported in 2012 and two large-scale outbreaks took place in Saudi Arabia (2014) and South Korea (2015). From 2012 through the end of 2018, 2279 cases were reported to WHO, with a fatality rate of 35% (806 deaths). However, no specific antiviral or vaccine against MERS-CoV infection is currently available. Further investigation of virus‑host interaction may provide mechanistic insights into the development of therapeutic agents. In this study, we performed a genome-wide CRISPR-Cas9 screen to identify host dependency factors for MERS-CoV infection in a cultured cell model. From this positive-selection screen, we identified 13 host protein factors while one of them is the known receptor (DPP4) for the MERS-CoV. Next, we characterized one of these host dependency factors, PTBP1, and investigated its role in the MERS-CoV infection. Interestingly, we found that PTBP1 does not directly regulate the MERS-CoV viral replication, but limits the viral entry through the negative regulation of DPP4 receptor expression. Therefore targeting PTBP1 expression may help to restrict the MERS-CoV infection through the downregulation of its receptor DPP4. This study was supported by Research Grant Council–Theme‑based Research Scheme (T11-707/15-R).