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

To prioritize the list of ncRNAs and genes within the QTL, the relationship between RNA 65 transcript levels and viral titer in the lung was examined. Sixty seven preCC mice had both 66 microarray and titer data available, of which sixty had titers above the limit of detection 67 (Gralinski et al., 2015) . Of the 74 candidate genes, 54 had one or more probes on the 68 microarray (Table S4) Table S5 ). Using 70 infection data from the founder mice, Muc4 RNA expression levels mimicked the allelic effects 71 of the QTL with PWK/PhJ mice exhibiting low Muc4 RNA levels (Fig. 1C ). Other potential 72 targets included Lrrc33, Sec22a, Parp14, and Ildr1; however, these genes either have little 73 known linkage to viral replication and the immune response (e.g., Lrrc33, Sec22a, and Ildr1) or 74 the directionality of the correlation did not support their relationship to viral titer in the lung 75 (Parp14). For Muc4, high levels of expression at mucosal surfaces and in various human 76 cancers have been reported (Andrianifahanana et al., 2001; Chaturvedi et al., 2008; Kamikawa 77 et al., 2015) . In addition, Muc4 plays a role in cell and anti-apoptotic signaling (Chaturvedi et al., 78 2008; Funes et al., 2006; Moniaux et al., 2007) . Together, the data suggest that Muc4 may play 79 a role in viral titers at day 4 post SARS-CoV infection. 80