Mucin 4 Protects Female Mice from Coronavirus Pathogenesis

Jessica A. Plante; Kenneth S. Plante; Lisa E. Gralinski; Anne Beall; Martin T. Ferris; Daniel Bottomly; Richard Green; Shannon K. McWeeney; Mark T. Heise; Ralph S. Baric; Vineet D. Menachery

anti-inflammatory (Kato K et al., 2014; Li Y et al., 2010; Ueno K et al., 2008) . We chose Muc4 192 as our priority candidate gene for follow up, with the initial hypothesis that Muc4 suppressed 193 apoptosis and possible the interferon response, and that its absence in a Muc4 -/mouse would 194 therefore lead to increased apoptosis and inflammation, thereby inhibiting Our validation utilized a Muc4 -/mouse and confirmed a role for Muc4 in protection from 197 SARS-CoV-and CHIKV-induced disease and pathogenesis. However, we found essentially no 198 . 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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/10.1101/2020.02.19.957118 doi: bioRxiv preprint differences in SARS-CoV viral load in the Muc4 -/mouse strain compared to WT mice. This may 199 be due to sex (discussed more below), differences between naturally occurring SNPs impacting 200 gene structure and expression and ablative knockouts, or the effects of overall genetic 201 background on given gene variants (Leist et al., 2016) . The SARS-CoV titer QTL on 202 The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.19.957118 doi: bioRxiv preprint (Channappanavar et al., 2017) . Furthermore, epidemiological data from both SARS-CoV and 224 SARS-CoV-2 indicate that human females may be more resistant than human males (Chen et 225 al., 2020; Huang et al., 2020; Karlberg et al., 2004; Leong et al., 2006)