title: Major and minor group rhinoviruses elicit differential signaling and cytokine responses as a function of receptor-mediated signal transduction.
abstract: Major- and minor-group human rhinoviruses (HRV) enter their host by binding to the cell surface molecules ICAM-1 and LDL-R, respectively, which are present on both macrophages and epithelial cells. Although epithelial cells are the primary site of productive HRV infection, previous studies have implicated macrophages in establishing the cytokine dysregulation that occurs during rhinovirus-induced asthma exacerbations. Analysis of the transcriptome of primary human macrophages exposed to major- and minor-group HRV demonstrated differential gene expression. Alterations in gene expression were traced to differential mitochondrial activity and signaling pathway activation between two rhinovirus serotypes, HRV16 (major-group) and HRV1A (minor-group), upon initial HRV binding. Variances in phosphorylation of kinases (p38, JNK, ERK5) and transcription factors (ATF-2, CREB, CEBP-alpha) were observed between the major- and minor-group HRV treatments. Differential activation of signaling pathways led to changes in the production of the asthma-relevant cytokines CCL20, CCL2, and IL-10. This is the first report of genetically similar viruses eliciting dissimilar cytokine release, transcription factor phosphorylation, and MAPK activation from macrophages, suggesting that receptor use is a mechanism for establishing the inflammatory microenvironment in the human airway upon exposure to rhinovirus.
authors.affiliation: Department of Chemistry, Lawrence University, Appleton, Wisconsin, United States of America.
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Schuler
authors.affiliation: Department of Chemistry, Lawrence University, Appleton, Wisconsin, United States of America; Department of Microbiology & Immunology, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Schreiber
authors.affiliation: Department of Chemistry, Lawrence University, Appleton, Wisconsin, United States of America.
authors.forename: Luyuan
authors.initials: L
authors.lastname: Li
authors.affiliation: Division of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Michal
authors.initials: M
authors.lastname: Mokry
authors.affiliation: Department of Chemistry, Lawrence University, Appleton, Wisconsin, United States of America.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Kingdon
authors.affiliation: Department of Chemistry, Lawrence University, Appleton, Wisconsin, United States of America.
authors.forename: Dana N
authors.initials: DN
authors.lastname: Raugi
authors.affiliation: Department of Chemistry, Lawrence University, Appleton, Wisconsin, United States of America.
authors.forename: Cosonya
authors.initials: C
authors.lastname: Smith
authors.affiliation: Department of Chemistry, Lawrence University, Appleton, Wisconsin, United States of America.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Hameister
authors.affiliation: Department of Microbiology & Immunology, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Vincent R
authors.initials: VR
authors.lastname: Racaniello
authors.affiliation: Department of Chemistry, Lawrence University, Appleton, Wisconsin, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hall
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D053078:Membrane Potential, Mitochondrial; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D010850:Picornaviridae Infections / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011991:Receptors, Virus / Q000378:metabolism*; D012229:Rhinovirus / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014779:Virus Replication
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D011991:Receptors, Virus; D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases
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