title: Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells.
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.
authors.affiliation: Departments of Immunobiology and Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520;
authors.forename: Ellen F
authors.initials: EF
authors.lastname: Foxman
authors.affiliation: Departments of Immunobiology and.
authors.forename: James A
authors.initials: JA
authors.lastname: Storer
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, Yale University, New Haven, CT 06520; and.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Fitzgerald
authors.affiliation: Department of Ecology and Evolutionary Biology, and.
authors.forename: Bethany R
authors.initials: BR
authors.lastname: Wasik
authors.affiliation: Department of Biostatistics, Yale University School of Public Health, New Haven, CT 06520.
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Biostatistics, Yale University School of Public Health, New Haven, CT 06520.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Ecology and Evolutionary Biology, and.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Turner
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, Yale University, New Haven, CT 06520; and.
authors.forename: Anna Marie
authors.initials: AM
authors.lastname: Pyle
authors.affiliation: 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.
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D007113:Immunity, Innate; D051379:Mice; D008969:Molecular Sequence Data; D012229:Rhinovirus / Q000276:immunology* / Q000502:physiology; D013696:Temperature; D014132:Trachea / Q000821:virology*; D014779:Virus Replication
keywords: RIG-I; airway; common cold; innate immunity; rhinovirus