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 further evaluate damage to the lung following infection, whole body plethysmography 119 was utilized to examine changes in pulmonary function (Fig. 5 ). Using only females, both WT 120 and Muc4 -/mice were challenged with a lower dose (10 4 PFU) to ensure their survival over the 121 full six day time course required to observe the onset, peak, and recovery of disordered lung 122 function following SARS-CoV challenge in mice (Menachery et al., 2015a) . Examining airway 123 resistance (penH), the time to peak expiratory flow relative to total expiratory time (rPEF), and 124 mid-tidal expiratory flow (EF50), all three measurements had statistically significant differences 125 between SARS-CoV-infected and mock-infected mice within the Muc4 -/and WT groups 126 (Supplementary Table S3 ). However, no Muc4-dependent differences in either penH (Fig. 5A ) 127 or rPEF (Fig. 5B ) were observed following SARS-CoV infection. In contrast, while not reaching 128 statistical significance, EF50 trended higher in the Muc4 -/mice as compared to WT mice, 129 peaking at day three post-infection (Fig. 5C) . These results show a shift in the early breathing 130 curve in Muc4 -/mice with more rapid exhalation and more labored breathing. These findings 131 may have been exacerbated with the original, higher dose, but that experiment was precluded 132 by the limited survival of Muc4 -/mice. Overall, the whole body plethysmography data indicate 133 more difficult breathing for female Muc4 -/mice relative to their WT counterparts following 134