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

In addition, expression of endosomal cathepsins, cell surface transmembrane proteases 87 (TMPRSS), furin, and trypsin differentially modulates the entry of different human CoVs (31-88 35) . other human CoVs, HCoV-OC43 hijacks human IFITM2 or IFITM3 as entry factors to facilitate 98 its infection of host cells (42, 43) . We also demonstrated recently that GILT suppresses the entry 99 of SARS-CoV, but not other human CoVs (38) . As reported herein, in our efforts to identify host 100 efficiency of HCoV-OC43pp infection in C3A cultures is approximately 50 folds higher than 124 that in HepG2 cultures. These results clearly indicate that the differential susceptibility is 125 attributed to the distinct ability of the two cell lines to support the infectious entry of 128 IFITM proteins modulate HCoV-OC43 infection of C3A and HepG2 cells in a similar 129 extent. We reported previously that IFITM proteins differentially modulate HCoV-OC43 entry 130 into target cells. While IFITM1 inhibits the virus entry, IFITM2 and IFITM3 enhance the cellular 131 entry of this virus (42). To investigate whether the differential expression of IFITM proteins in 132 the two cell lines is responsible for their difference in HCoV-OC43 infection efficiency, we 133 examined IFITM protein expression by Western blot assays and found the two hepatoma cell 134 lines expressed similar levels of IFITM1 and IFITM2/3 (Fig. 1B) . Because the C-terminal 135 variable regions of IFITM1 and IFITM3 control the inhibition and enhancement of HCoV-OC43 136 entry (42), respectively, we further compared the effects of IFITM1 and C-terminal region 137 exchanged IFITM proteins on the virus infection. As shown in Fig. 3 , in spite of their distinct 138 susceptibility, expression of IFITM1-EX2, a mutant IFITM1 protein with its C-terminal domain 139