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

AmphoB can bind cholesterol in cell membranes to increase membrane fluidity and planarity and 290 consequentially rescue IFITM inhibition of virus entry (52). Interestingly, AmphoB only 291 neutralize the antiviral effects of IFITM2 and IFITM3, but has little effect on IFITM1 restriction 292 of virus entry (52). While IFITM1 is predominantly located in the plasma membrane or early 293 endosomes, IFITM2 and 3 are mainly localized in the later endosomes and lysosomes. Due to 294 their differential subcellular localization, IFITM1 mainly restricts the viruses that enter the cells 295 at cell surface or in the early endosomes, such as parainfluenza viruses and hepatitis C virus (59, 296 60), IFITM2 and 3 primarily restrict the infection of viruses that enter the cells at later 297 endosomes and/or lysosomes (43, 61, 62). Because AmphoB is endocytosed quite rapidly 298 leading to its concentration in the late endosomes and lysosomes, it more efficiently alleviates 299 the effect of IFITM2 and 3, but not IFITM1, on virus entry (52). Similarly, the failure of 300