kjgmtlv0

Property	Value
?: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. Author Summary Respiratory viruses from diverse families co-circulate in human populations and are frequently detected within the same host. Though clinical studies suggest that coinfection by more than one unrelated respiratory virus may alter disease severity, animal models in which we can control the doses, timing, and strains of coinfecting viruses are critical to understand how coinfection affects disease severity. In this study, we compared gene expression and immune cell recruitment between two pairs of coinfecting viruses (RV/PR8 and RV/PVM) that both result in reduced severity compared to infection by PR8 or PVM alone in mice. Reduced disease severity was associated with suppression of inflammatory responses in the lungs. However, differences in disease kinetics and host and viral gene expression suggest that protection by coinfection with RV may be due to distinct molecular mechanisms.
is ?:annotates of	<https://research.tib.eu/covid-19/entity/kjgmtlv0_hasAnnotation_C0035473> <https://research.tib.eu/covid-19/entity/kjgmtlv0_hasAnnotation_C0597404> <https://research.tib.eu/covid-19/entity/kjgmtlv0_hasAnnotation_C1155266>
?:creator	<https://research.tib.eu/covid-19/entity/Van_Leuven%2C_James_T.%3B_Gonzalez%2C_Andres_J.%3B_Wixom%2C_Alexander_Q.%3B_Clary%2C_John_L.%3B_Ridenhour%2C_Benjamin_J.%3B_Miller%2C_Craig_R.%3B_Miura%2C_Tanya_A.>
?:doi	<https://research.tib.eu/covid-19/entity/10.1101/2020.11.06.371005>
?:doi	10.1101/2020.11.06.371005
?:externalLink	<https://doi.org/10.1101/2020.11.06.371005>
?:journal	bioRxiv
?:license	biorxiv
?:pdf_json_files	document_parses/pdf_json/1bbb393c94dc6165d7a75101ba740b5a47fd9dde.json
?:publication_isRelatedTo_Disease	<https://research.tib.eu/covid-19/entity/COVID-19>
is ?:relation_isRelatedTo_publication of	<https://research.tib.eu/covid-19/entity/kjgmtlv0_HAS_C1155266_AFFECTS_C0597404>
?:sha_id	<https://research.tib.eu/covid-19/entity/1bbb393c94dc6165d7a75101ba740b5a47fd9dde>
?:source	BioRxiv
?:title	Rhinovirus reduces the severity of subsequent respiratory viral infections, which is associated with dampened inflammatory responses
?:type	<https://research.tib.eu/covid-19/vocab/Publication>
?:year	2020-11-06

Property

Value

?: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. Author Summary Respiratory viruses from diverse families co-circulate in human populations and are frequently detected within the same host. Though clinical studies suggest that coinfection by more than one unrelated respiratory virus may alter disease severity, animal models in which we can control the doses, timing, and strains of coinfecting viruses are critical to understand how coinfection affects disease severity. In this study, we compared gene expression and immune cell recruitment between two pairs of coinfecting viruses (RV/PR8 and RV/PVM) that both result in reduced severity compared to infection by PR8 or PVM alone in mice. Reduced disease severity was associated with suppression of inflammatory responses in the lungs. However, differences in disease kinetics and host and viral gene expression suggest that protection by coinfection with RV may be due to distinct molecular mechanisms.

is ?:annotates of