title: Novel immune genes associated with excessive inflammatory and antiviral responses to rhinovirus in COPD.
abstract: BACKGROUND
  Rhinovirus (RV) is a major cause of chronic obstructive pulmonary disease (COPD) exacerbations, and primarily infects bronchial epithelial cells. Immune responses from BECs to RV infection are critical in limiting viral replication, and remain unclear in COPD. The objective of this study is to investigate innate immune responses to RV infection in COPD primary BECs (pBECs) in comparison to healthy controls.
  
  
  METHODS
  Primary bronchial epithelial cells (pBECs) from subjects with COPD and healthy controls were infected with RV-1B. Cells and cell supernatant were collected and analysed using gene expression microarray, qPCR, ELISA, flow cytometry and titration assay for viral replication.
  
  
  RESULTS
  COPD pBECs responded to RV-1B infection with an increased expression of antiviral and pro-inflammatory genes compared to healthy pBECs, including cytokines, chemokines, RNA helicases, and interferons (IFNs). Similar levels of viral replication were observed in both disease groups; however COPD pBECs were highly susceptible to apoptosis. COPD pBECs differed at baseline in the expression of 9 genes, including calgranulins S100A8/A9, and 22 genes after RV-1B infection including the signalling proteins pellino-1 and interleukin-1 receptor associated kinase 2. In COPD, IFN-β/λ1 pre-treatment did not change MDA-5/RIG-I and IFN-β expression, but resulted in higher levels IFN-λ1, CXCL-10 and CCL-5. This led to reduced viral replication, but did not increase pro-inflammatory cytokines.
  
  
  CONCLUSIONS
  COPD pBECs elicit an exaggerated pro-inflammatory and antiviral response to RV-1B infection, without changing viral replication. IFN pre-treatment reduced viral replication. This study identified novel genes and pathways involved in potentiating the inflammatory response to RV in COPD.
authors: Priority Research Centre for Asthma and Respiratory Diseases, The University of Newcastle, Callaghan, NSW, Australia. katherine.baines@newcastle.edu.au
authors: Katherine J
authors: KJ
authors: Baines
authors: Alan C-Y
authors: AC
authors: Hsu
authors: Melinda
authors: M
authors: Tooze
authors: Lakshitha P
authors: LP
authors: Gunawardhana
authors: Peter G
authors: PG
authors: Gibson
authors: Peter A B
authors: PA
authors: Wark
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016000:Cluster Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression / Q000502:physiology; D016678:Genome / Q000235:genetics; D006801:Humans; D007109:Immunity / Q000235:genetics*; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000209:etiology* / Q000235:genetics*; D018836:Inflammation Mediators / Q000378:metabolism; D046228:Microarray Analysis; D010447:Peptide Hydrolases / Q000235:genetics; D010850:Picornaviridae Infections / Q000150:complications* / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000235:genetics* / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D012129:Respiratory Function Tests; D012229:Rhinovirus / Q000276:immunology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D018836:Inflammation Mediators; D010447:Peptide Hydrolases
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