title: Human respiratory syncytial virus viroporin SH: a viral recognition pathway used by the host to signal inflammasome activation.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) remains the leading cause of serious viral bronchiolitis and pneumonia in infants and young children throughout the world. The burden of disease is significant, with 70% of all infants being infected with RSV within the first year of their life. 40% of those children discharged from hospital have recurrent, repeated respiratory symptoms and wheezing for at least 10 years. The infection is also an important illness in the elderly and immunocompromised individuals. Ongoing symptoms relate to continued lung inflammation. One cytokine that is associated with RSV infection is IL-1β, but the mechanism of activation remain unclear.
  
  
  OBJECTIVE
  In the current study, we set out to decipher the molecular mechanisms of RSV-induced inflammasome activation.
  
  
  RESULTS
  Using deletion mutants of the virus and measuring IL-1β secretion, as well as caspase 1 expression via western blotting, we demonstrate that the NLRP3 inflammasome is activated through the small hydrophobic (SH) RSV viroporin which induces membrane permeability to ions or small molecules. Confocal microscopy revealed that during virus infection, SH seems to accumulate within lipid rafts in the Golgi compartments.
  
  
  CONCLUSIONS
  Upon RSV infection, SH gets localised in the cell membranes and intracellular organelle membranes, and then induces permeability by disrupting membrane architecture, thus leading us to believe that formation of viral ion channels in lipid bilayers of cells is a viral recognition pathway used by the host to signal inflammasome activation.
authors.affiliation: Department of Child Health, School of Medicine, University Hospital of Wales Heath Park, Cardiff University, Cardiff, UK. TriantafilouM@cardiff.ac.uk
authors.forename: Kathy
authors.initials: K
authors.lastname: Triantafilou
authors.forename: Satwik
authors.initials: S
authors.lastname: Kar
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Vakakis
authors.forename: Sailesh
authors.initials: S
authors.lastname: Kotecha
authors.forename: Martha
authors.initials: M
authors.lastname: Triantafilou
mesh_terms: D000328:Adult; D001990:Bronchiolitis, Viral / Q000235:genetics / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology; D008297:Male; D018613:Microscopy, Confocal; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011024:Pneumonia, Viral / Q000378:metabolism / Q000503:physiopathology; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000503:physiopathology; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics* / Q000502:physiology; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D012367:RNA, Viral