Background:The mechanism of influenza mediated TGF␤ activation, and its role in pathogenesis is unclear. Results: H1N1 infection induced ␣v␤6-dependent TGF␤ activity in iHBECs and increased epithelial cell death and collagen deposition in vivo. Conclusion: ␣v␤6 integrin-mediated TGF␤ activation is involved in cell death and fibrogenesis following virus-induced epithelial injury. Significance: Viral infection may promote acute exacerbations of fibrotic lung disease.

Schmallenberg virus (SBV) caused a large scale epidemic in Europe from 2011 to 2013, infecting ruminants and causing foetal deformities after infection of pregnant animals. The main impact of the virus was financial loss due to restrictions on trade of animals, meat and semen. Although effective vaccines were produced, their uptake was never high. Along with the subsequent decline in new SBV infections and natural replacement of previously exposed livestock, this has resulted in a decrease in the number of protected animals. Recent surveillance has shown that a large population of naïve animals is currently present in Europe and that the virus is circulating at a low level. These changes in animal status, in combination with favourable conditions for insect vectors, may open the door to the re-emergence of SBV and another large scale outbreak in Europe. This review details the potential and preparedness for SBV re-emergence in Europe, discusses possible co-ordinated sentinel monitoring programmes for ruminant seroconversion and the presence of SBV in the insect vectors, and provides an overview of the economic impact associated with diagnosis, control and the effects of non-vaccination.

Heterotrimeric guanine nucleotide-binding protein (G protein) signaling links hundreds of G protein-coupled receptors (GPCRs) with four G protein signaling pathways. Two of these, one mediated by G q and G 11 (G q/11 ) and the other by G 12 and G 13 (G 12/13 ), are implicated in the force-dependent activation of transforming growth factor-β (TGFβ) in lung epithelial cells. Reduced TGFβ activation in alveolar cells leads to emphysema, whereas enhanced TGFβ activation promotes acute lung injury and idiopathic pulmonary fibrosis. Therefore, precise control of alveolar TGFβ activation is essential for alveolar homeostasis. Here, we investigated the involvement of the G q/11 and G 12/13 pathways in epithelial cells in generating active TGFβ and regulating alveolar inflammation. Mice deficient in both Gα q and Gα 11 developed inflammation that was primarily caused by alternatively activated (M2-polarized) macrophages, enhanced matrix metalloprotease 12 (MMP12) production, and age-related alveolar airspace enlargement consistent with emphysema. Mice with impaired G q/11 signaling had reduced stretch-mediated generation of TGFβ by epithelial cells and enhanced macrophage MMP12 synthesis, but were protected from the effects of ventilator-induced lung injury. Furthermore, synthesis of the cytokine interleukin-33 (IL-33) was increased in these alveolar epithelial cells, resulting in the M2-type polarization of alveolar macrophages independently of the effect on TGFβ. Our results suggest that alveolar G q/11 signaling maintains alveolar homeostasis, and likely independently increases TGFβ activation in response to mechanical stress of the epithelium and decreases epithelial IL-33 synthesis.Together, these findings suggest that disruption of G q/11 signaling promotes inflammatory emphysema but protects against mechanically induced lung injury.