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Front Immunol . Priming With Rhinovirus Protects Mice Against a Lethal Pulmonary Coronavirus Infection

tetano

Editor, Senior Moderator
Front Immunol


. 2022 May 30;13:886611.
doi: 10.3389/fimmu.2022.886611. eCollection 2022.
Priming With Rhinovirus Protects Mice Against a Lethal Pulmonary Coronavirus Infection


Garrison Cox[SUP] 1 [/SUP], Andres J Gonzalez[SUP] 1 2 [/SUP], Emmanuel C Ijezie[SUP] 1 [/SUP], Andres Rodriguez[SUP] 1 [/SUP], Craig R Miller[SUP] 1 2 [/SUP], James T Van Leuven[SUP] 1 2 [/SUP], Tanya A Miura[SUP] 1 2 [/SUP]



Affiliations

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.

Keywords: coronaviral infection; coronavirus; interferon; mouse hepatitis virus; mouse model; respiratory virus co-infection; rhinovirus.
 
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