bioRxiv preprint doi: https://doi.org/10.1101/2020.08.11.246678; this version posted August 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Opposing activities of IFITM proteins in SARS-CoV-2 infection Guoli Shi1*, Adam D. Kenney2,3*, Elena Kudryashova3,4, Lizhi Zhang2,3, Luanne Hall-Stoodley2, Richard T. Robinson2, Dmitri S. Kudryashov3,4, Alex A. Compton1,#, and Jacob S. Yount2,3,# 1HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD, USA. 2Department of Microbial Infection and Immunity, The Ohio State University College of Medicine, Columbus, OH, USA 3Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University, Columbus, OH, USA 4Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA *These authors contributed equally to this work #Address correspondence to Alex A. Compton,
[email protected], and Jacob S. Yount,
[email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.11.246678; this version posted August 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Interferon-induced transmembrane proteins (IFITMs) restrict infections by many viruses, but a subset of IFITMs enhance infections by specific coronaviruses through currently unknown mechanisms. Here we show that SARS-CoV-2 Spike-pseudotyped virus and genuine SARS- CoV-2 infections are generally restricted by expression of human IFITM1, IFITM2, and IFITM3, using both gain- and loss-of-function approaches.