LY6E Restricts the Entry of Human Coronaviruses, including the currently pandemic SARS-CoV-2

Xuesen Zhao; Shuangli Zheng; Danying Chen; Mei Zheng; Xinglin Li; Guoli Li; Hanxin Lin; Jinhong Chang; Hui Zeng; Ju-Tao Guo

replaced with the C-terminal domain of IFITM3 (42), and IFITM3-EX2, a mutant IFITM3 140 protein with its C-terminal domain replaced with the C-terminal domain of IFITM1 (42), 141 significantly enhanced and inhibited HCoV-OC43 infection of both cell lines, respectively, as 142 evidenced by the significant changes in infected cell percentage (Fig. 3A) , reduced viral 143 nucleocapsid protein expression (Fig. 3B ), intracellular RNA accumulation (Fig. 3C ) and yields 144 of progeny virus production (Fig. 3D) . Moreover, pseudotyped lentiviral infection assay further 145 demonstrated that IFITM1, IFITM1-EX2 and IFITM3-EX2 modulated HCoV-OC43 envelope 146 . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.02.021469 doi: bioRxiv preprint proteins mediated entry in a similar extent in the two cell lines (Fig. 3E) . Accordingly, we 147 concluded that IFITM proteins were not responsible for the observed differential susceptibility of 148 the two hepatoma cell lines to HCoV-OC43 infection. 149 150 LY6E inhibits the entry mediated by human CoV envelope spike proteins and is 151 responsible for the differential susceptibility of C3A and HepG2 cells to HCoV-OC43 152 infection. In order to identify host cellular proteins that may enhance HCoV-OC43 infection of 153 C3A cells or suppress the virus entry into HepG2 cells, we first compared the expression of 154 several cellular genes with known activity to restrict or enhance virus entry into target cells. As 155 shown in Fig. 4A , we found that ADAP2, GILT and LY6E mRNA expressed at significantly 156 higher levels in HepG2 cells. While the expression of ADAP2 and GILT did not inhibit HCoV-157