Priming With Rhinovirus Protects Mice Against a Lethal Pulmonary Coronavirus Infection
Garrison Cox, Andrés J. Gonzalez, Emmanuel C. Ijezie, Andrés Rodríguez, Craig R. Miller, James T. Van Leuven, Tanya A. Miura
Abstract
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 expression of antiviral type I interferon, IFN-β, was more robust in mice infected with MHV-1 alone. We further showed that signaling through the type I interferon receptor 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 upon MHV-1 infection. Although MHV-1 replication was reduced in RV-primed mice, RV did not inhibit MHV-1 replication in coinfected lung epithelial cells in vitro . In summary, RV-mediated priming in the respiratory tract reduces viral replication, inflammation, and tissue damage, and prevents mortality of a pulmonary coronavirus infection in mice. These results contribute to our understanding of how distinct respiratory viruses interact with the host to affect disease pathogenesis, which is a critical step in understanding how respiratory viral coinfections impact human health.