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Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature.

ABSTRACT: Most strains of rhinovirus (RV), the common cold virus, replicate better at cool temperatures found in the nasal cavity (33-35 °C) than at lung temperature (37 °C). Recent studies found that although 37 °C temperature suppressed RV growth largely by engaging the type 1 IFN response in infected epithelial cells, a significant temperature dependence to viral replication remained in cells devoid of IFN induction or signaling. To gain insight into IFN-independent mechanisms limiting RV replication at 37 °C, we studied RV infection in human bronchial epithelial cells and H1-HeLa cells. During the single replication cycle, RV exhibited temperature-dependent replication in both cell types in the absence of IFN induction. At 37 °C, earlier signs of apoptosis in RV-infected cells were accompanied by reduced virus production. Furthermore, apoptosis of epithelial cells was enhanced at 37 °C in response to diverse stimuli. Dynamic mathematical modeling and B cell lymphoma 2 (BCL2) overexpression revealed that temperature-dependent host cell death could partially account for the temperature-dependent growth observed during RV amplification, but also suggested additional mechanisms of virus control. In search of a redundant antiviral pathway, we identified a role for the RNA-degrading enzyme RNAseL. Simultaneous antagonism of apoptosis and RNAseL increased viral replication and dramatically reduced temperature dependence. These findings reveal two IFN-independent mechanisms active in innate defense against RV, and demonstrate that even in the absence of IFNs, temperature-dependent RV amplification is largely a result of host cell antiviral restriction mechanisms operating more effectively at 37 °C than at 33 °C.

SUBMITTER: Foxman EF

PROVIDER: S-EPMC4968739 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature.

Foxman Ellen F EF Storer James A JA Vanaja Kiran K Levchenko Andre A Iwasaki Akiko A

Proceedings of the National Academy of Sciences of the United States of America 20160711 30

Most strains of rhinovirus (RV), the common cold virus, replicate better at cool temperatures found in the nasal cavity (33-35 °C) than at lung temperature (37 °C). Recent studies found that although 37 °C temperature suppressed RV growth largely by engaging the type 1 IFN response in infected epithelial cells, a significant temperature dependence to viral replication remained in cells devoid of IFN induction or signaling. To gain insight into IFN-independent mechanisms limiting RV replication a ...[more]

PMID: 27402752

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Project description:The Arabian Peninsula (Arabia) is among the places to have experienced the greatest amount of warming during recent decades, and this trend is projected to continue. Specifics related to the characteristics (frequency, duration, and intensity) of extreme temperature events (ETEs) over Arabia as a whole are either largely outdated or limited only to specific areas. The seasonal ETE definitions commonly used in local studies are neither climatological- nor phenomenon-based. Using a novel and straightforward framework, the seasons of four extreme temperature types (extreme warm days/nights (EWDs/EWNs) and extreme cold days/nights (ECDs/ECNs)) were identified on the simultaneous basis of event occurrence and impact times. Assessments of ETE frequency, duration, and intensity and their recent changes were then provided based on the most recent climate data (1991-2020). Results showed that the use of traditional seasonal definitions (e.g., meteorological seasons) tends to assume a spatiotemporal homogeneity in the seasonality of ETEs and their potential risk levels throughout the year. The developed framework distinguished months with events that have larger potential impacts together with their local seasons. ETE seasons were found to vary at the regional and local scales and are better defined at both the local and phenomenon levels. Early extreme warm events were hotter, and those at locations with longer local warm seasons demonstrated higher intensities. ECDs tended to be more frequent at coastal locations, whereas ECNs were more frequent over southwestern Arabia. Early and late extreme cold events were much colder than those occurring mid-season. Trend analyses revealed generally increasing regional trends in the frequency of extreme warm events, whereas extreme cold events have declined. The duration (i.e., consecutive occurrences) and intensity of EWNs have been increasing at more locations, suggesting that urgent attention is needed within such an arid and hot climate type in which nighttime stress relief is already very limited.

Dataset Information

Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature.

Publications

Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature.

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