Transcriptome response of murine alveolar epithelial cells to infection by three unrelated respiratory viruses commonly studied in mouse models II

Rhinoviruses (RV) have been shown to inhibit subsequent infection by heterologous respiratory viruses, including influenza viruses and severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). To better understand the mechanisms whereby RV protects against pulmonary coronavirus infection, we used a native murine virus, mouse hepatitis virus strain 1 (MHV-1), that causes severe disease in the lungs of infected mice. We found that priming of the respiratory tract with RV completely prevented mortality and reduced morbidity of a lethal MHV-1 infection. Replication of MHV-1 was reduced in RV-primed mouse lungs although type I interferon (IFN-b) expression was more robust in mice infected with MHV-1 alone. We further showed that type I IFN signaling was required for survival of mice given a non-lethal dose of MHV-1. RV-primed mice had reduced pulmonary inflammation and hemorrhage and influx of leukocytes, especially neutrophils, in the airways. RV-mediated priming in the respiratory tract protects against a lethal pulmonary coronavirus infection in mice. This model can be used to understand how heterologous viruses impact each other during coinfection of the respiratory tract. Microarray analysis of mouse epithelial cells infected by combinations of three viruses. Infections done in triplicate. RNA extracted at 12 and 24 hours post infection.