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 to lymphocytes, LY6E mRNA can also be detected in liver, spleen, uterus, ovary, 227 lung, and brain and its expression can be induced by type I IFN in a cell-type specific manner 228 Second, in addition to GPI anchor, the evolutionally conserved amino acid residue L36 is 256 also required for both the enhancement and restriction of virus entry into target cells by LY6E 257 ( Fig. 6 ) (48). It can be speculated that this specific residue may mediate an interaction with other 258 cellular membrane proteins to module viral entry. The fact that LY6E enhances viral infectivity 259 in a cell type-specific manner, with the strongest phenotype in cells of fibroblast and monocytic 260 . 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 lineages (48), does indicate the involvement of other host cellular factors. Variations in the 261 abundance of expression, as well as the localization of LY6E and its associated proteins or lipids, 262 may explain the differential effects of LY6E on the infection of different viruses in different cell 263 types ( Fig. 4 and 7) . However, LY6E enhancement of RNA virus infection appears to be 264 independent of type I interferon response and other ISG expression (48) CoV-2pp and HCoV-NL63pp, that share the ACE2 receptor, does not support such a hypothesis 282 (Fig. 4) . 283