title: Human Metapneumovirus Infection in Chronic Obstructive Pulmonary Disease: Impact of Glucocorticosteroids and Interferon.
abstract: Human metapneumovirus (hMPV) infection is implicated in exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Research into the pathogenesis of infection is restricted to animal models, and information about hMPV replication and inflammatory and immune responses in human disease is limited.
  
  
  
  Human primary bronchial epithelial cells (PBECs) from healthy and asthmatic subjects and those with COPD were infected with hMPV, with or without glucocorticosteroid (GCS) exposure. Viral replication, inflammatory and immune responses, and apoptosis were analyzed. We also determined whether adjuvant interferon (IFN) can blunt hMPV infection in vitro and in a murine model.
  
  
  
  hMPV infected human PBECs and viral replication was enhanced in cells from patients with COPD. The virus induced gene expression of IFN-stimulated gene 56 (ISG56) and IFN-β, as well as IFN-γ-inducible protein 10 (IP-10) and regulated on activation, normal T cell expressed and secreted (RANTES), and more so in cells from patients with COPD. GCS exposure enhanced hMPV replication despite increased IFN expression. Augmented virus replication associated with GCS was mediated by reduced apoptosis via induction of antiapoptotic genes. Adjuvant IFN treatment suppressed hMPV replication in PBECs and reduced hMPV viral titers and inflammation in vivo.
  
  
  
  hMPV infects human PBECs, eliciting innate and inflammatory responses. Replication is enhanced by GCS and adjuvant IFN is an effective treatment, restricting virus replication and proinflammatory consequences of hMPV infections.
authors.affiliation: Monash Lung & Sleep, Monash Medical Centre.|Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, and.|Department of Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Melbourne.|Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kan-O
authors.affiliation: Faculty of Applied Science, University of Canberra.
authors.forename: Ruben
authors.initials: R
authors.lastname: Ramirez
authors.affiliation: Monash Lung & Sleep, Monash Medical Centre.
authors.forename: Martin I
authors.initials: MI
authors.lastname: MacDonald
authors.affiliation: Institute for Glycomics, Griffith University, Southport, and.
authors.forename: Michael
authors.initials: M
authors.lastname: Rolph
authors.affiliation: Institute for Glycomics, Griffith University, Southport, and.
authors.forename: Penny A
authors.initials: PA
authors.lastname: Rudd
authors.affiliation: School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Spann
authors.affiliation: Institute for Glycomics, Griffith University, Southport, and.
authors.forename: Suresh
authors.initials: S
authors.lastname: Mahalingam
authors.affiliation: Monash Lung & Sleep, Monash Medical Centre.|Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, and.|Department of Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Melbourne.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Bardin
authors.affiliation: Monash Lung & Sleep, Monash Medical Centre.|Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, and.|Department of Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Melbourne.
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Thomas
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000821:virology; D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000821:virology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D029121:Metapneumovirus; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D018184:Paramyxoviridae Infections / Q000821:virology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000821:virology*; D020545:Respiratory Mucosa / Q000166:cytology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D005938:Glucocorticoids; D007371:Interferon-gamma
keywords: apoptosis; glucocorticosteroids; human metapneumovirus; human primary bronchial epithelial cells; innate immune response.; interferon