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Proc Natl Acad Sci U S A. 2015 Jan 20;112(3):827-32. doi: 10.1073/pnas.1411030112. Epub 2015 Jan 5.

Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells.

Author information

1
Departments of Immunobiology and Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520;
2
Departments of Immunobiology and.
3
Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, Yale University, New Haven, CT 06520; and.
4
Department of Ecology and Evolutionary Biology, and.
5
Department of Biostatistics, Yale University School of Public Health, New Haven, CT 06520.
6
Departments of Immunobiology and Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, Yale University, New Haven, CT 06520; and akiko.iwasaki@yale.edu.

Abstract

Most isolates of human rhinovirus, the common cold virus, replicate more robustly at the cool temperatures found in the nasal cavity (33-35 °C) than at core body temperature (37 °C). To gain insight into the mechanism of temperature-dependent growth, we compared the transcriptional response of primary mouse airway epithelial cells infected with rhinovirus at 33 °C vs. 37 °C. Mouse airway cells infected with mouse-adapted rhinovirus 1B exhibited a striking enrichment in expression of antiviral defense response genes at 37 °C relative to 33 °C, which correlated with significantly higher expression levels of type I and type III IFN genes and IFN-stimulated genes (ISGs) at 37 °C. Temperature-dependent IFN induction in response to rhinovirus was dependent on the MAVS protein, a key signaling adaptor of the RIG-I-like receptors (RLRs). Stimulation of primary airway cells with the synthetic RLR ligand poly I:C led to greater IFN induction at 37 °C relative to 33 °C at early time points poststimulation and to a sustained increase in the induction of ISGs at 37 °C relative to 33 °C. Recombinant type I IFN also stimulated more robust induction of ISGs at 37 °C than at 33 °C. Genetic deficiency of MAVS or the type I IFN receptor in infected airway cells permitted higher levels of viral replication, particularly at 37 °C, and partially rescued the temperature-dependent growth phenotype. These findings demonstrate that in mouse airway cells, rhinovirus replicates preferentially at nasal cavity temperature due, in part, to a less efficient antiviral defense response of infected cells at cool temperature.

KEYWORDS:

RIG-I; airway; common cold; innate immunity; rhinovirus

PMID:
25561542
PMCID:
PMC4311828
DOI:
10.1073/pnas.1411030112
[Indexed for MEDLINE]
Free PMC Article

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