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 Menachery

Research output: Contribution to journalArticlepeer-review

Abstract

Using incipient lines of the Collaborative Cross (CC), a murine genetic reference population, we previously identified a quantitative trait loci (QTL) associated with low SARS-CoV titer. In this study, we integrated sequence information and RNA expression of genes within the QTL to identify mucin 4 (Muc4) as a high priority candidate for controlling SARS-CoV titer in the lung. To test this hypothesis, we infected Muc4-/- mice and found that female, but not male, Muc4-/mice developed more weight loss and disease following infection with SARS-CoV. Female Muc4-/- mice also had more difficulty breathing despite reduced lung pathology; however, no change in viral titers was observed. Comparing across viral families, studies with chikungunya virus, a mosquito-borne arthralgic virus, suggests that Muc4’s impact on viral pathogenesis may be widespread. Although not confirming the original titer QTL, our data identifies a role for Muc4 in the SARS-CoV disease and viral pathogenesis.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Feb 20 2020

Keywords

  • 2019-nCoV
  • Coronavirus
  • Emergence
  • SARS-CoV
  • SARS-CoV-2
  • Zoonotic

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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