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Thorax 68:66-75 doi:10.1136/thoraxjnl-2012-202182
  • Respiratory infection

Human respiratory syncytial virus viroporin SH: a viral recognition pathway used by the host to signal inflammasome activation

  1. Martha Triantafilou
  1. Department of Child Health, School of Medicine, University Hospital of Wales Heath Park, Cardiff University, Cardiff, UK
  1. Correspondence to Dr Martha Triantafilou, Department of Child Health, School of Medicine, University Hospital of Wales Heath Park, Cardiff University, Cardiff CF14 4XN, UK; TriantafilouM{at}cardiff.ac.uk
  • Received 25 May 2012
  • Accepted 1 November 2012

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.

Objectives In the current study, we set out to decipher the molecular mechanisms of RSV-induced inflammasome activation.

Methods and 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.

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