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

CoVs including SARS-CoV-2, except for SARS-CoV ( Fig. 4C and 4D ). In addition, LY6E 160 enhanced the infection of IAVpp (Fig. 4D ). In agreement with our previous report, expression of 161 abolished the activity of LY6E to restrict the entry of human CoVs (Fig. 6 ). As anticipated, 180 N99A substitution that disrupts the addition of GPI anchor also abrogated the inhibitory effects 181 of LY6E on human CoV entry ( The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10. 1101 /2020 In this study, we further demonstrated that AmphoB treatment also efficiently attenuated the 215 restriction of IFITM3 on the infection of SARS-CoVpp, MERS-CoVpp, HCoV-NL63pp, HCoV-216 229Epp and IAVpp, but not LASVpp (Fig. 8A ). However, AmphoB treatment altered neither the 217 restriction activity of LY6E on the infection of human CoV spike protein-pseudotyped 218 lentiviruses nor the enhancement of LY6E on IAVpp infection (Fig. 8B ). These results strongly 219 imply that LY6E modulates virus entry via a distinct mechanism. 220 221 DISCUSSION 222 223 LY6E was initially identified as a cell surface marker to discriminate immature from 224 mature thymocytes subsets (53). The primary function of LY6E has been associated with 225 immune regulation, specifically in modulating T cell activation, proliferation, development (54). 226