Rhinovirus reduces the severity of subsequent respiratory viral infections by interferon-dependent and -independent mechanisms

Abstract

Coinfection by unrelated viruses in the respiratory tract is common and can result in changes in disease severity compared to infection by individual virus strains. We have previously shown that inoculation of mice with rhinovirus (RV) two days prior to inoculation with a lethal dose of influenza A virus (PR8), provides complete protection against mortality. In this study, we extend that finding to a second lethal respiratory virus, pneumonia virus of mice (PVM) and characterize the differences in inflammatory responses and host gene expression in single virus infected vs. coinfected mice. RV prevented mortality and weight loss associated with PVM infection, suggesting that RV-mediated protection is more effective against PVM than PR8. Major changes in host gene expression upon PVM infection were delayed compared to PR8, which likely provides a larger time frame for RV-induced gene expression to alter the course of disease. Overall, RV induced earlier recruitment of inflammatory cells, while these populations were reduced at later times in coinfected mice. Findings common to both coinfection conditions included upregulated expression of mucin-associated genes in RV/PR8 and RV/PVM compared to mock/PR8 and mock/PVM infected mice and dampening of inflammation-related genes late during coinfection. These findings, combined with differences in virus replication levels and disease severity, suggest that the suppression of inflammation in RV/PVM coinfected mice may be due to early suppression of viral replication, while in RV/PR8 coinfected mice may be due to a direct suppression of inflammation. Thus, a mild upper respiratory viral infection can reduce the severity of a subsequent severe viral infection in the lungs through virus-dependent mechanisms.

RSV protects bystander cells against IAV infection by triggering secretion of type I and type III interferons

“…Non-antigenic competitive interactions among respiratory viruses have been suggested based on clinical data analysis [12,13] and were recapitulated within animal models [14,15]. Two very recent studies [16,17] demonstrated that an innate immunity mechanism, specifically antiviral cytokine signaling, is implicated in the interference between RV and IAV: blocking the type-I interferon (IFN) response restores IAV replication following RV infection. Whereas type-I IFNs (IFNα and IFNβ) were originally discovered specifically because of their activity against the influenza virus [18], their roles in RSV infection and disease have been controversial [19][20][21][22][23][24][25].…”