[HTML][HTML] Role of host cellular proteases in the pathogenesis of influenza and influenza-induced multiple organ failure

H Kido, Y Okumura, E Takahashi, HY Pan… - … et Biophysica Acta (BBA …, 2012 - Elsevier
H Kido, Y Okumura, E Takahashi, HY Pan, S Wang, D Yao, M Yao, J Chida, M Yano
Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 2012Elsevier
Influenza A virus (IAV) is one of the most common infectious pathogens in humans. Since
the IVA genome does not have the processing protease for the viral hemagglutinin (HA)
envelope glycoprotein precursors, entry of this virus into cells and infectious organ tropism of
IAV are primarily determined by host cellular trypsin-type HA processing proteases. Several
secretion-type HA processing proteases for seasonal IAV in the airway, and ubiquitously
expressed furin and pro-protein convertases for highly pathogenic avian influenza (HPAI) …
Influenza A virus (IAV) is one of the most common infectious pathogens in humans. Since the IVA genome does not have the processing protease for the viral hemagglutinin (HA) envelope glycoprotein precursors, entry of this virus into cells and infectious organ tropism of IAV are primarily determined by host cellular trypsin-type HA processing proteases. Several secretion-type HA processing proteases for seasonal IAV in the airway, and ubiquitously expressed furin and pro-protein convertases for highly pathogenic avian influenza (HPAI) virus, have been reported. Recently, other HA-processing proteases for seasonal IAV and HPAI have been identified in the membrane fraction. These proteases proteolytically activate viral multiplication at the time of viral entry and budding. In addition to the role of host cellular proteases in IAV pathogenicity, IAV infection results in marked upregulation of cellular trypsins and matrix metalloproteinase-9 in various organs and cells, particularly endothelial cells, through induced pro-inflammatory cytokines. These host cellular factors interact with each other as the influenza virus–cytokine–protease cycle, which is the major mechanism that induces vascular hyperpermeability and multiorgan failure in severe influenza. This mini-review discusses the roles of cellular proteases in the pathogenesis of IAV and highlights the molecular mechanisms of upregulation of trypsins as effective targets for the control of IAV infection. This article is part of a Special Issue entitled: Proteolysis 50years after the discovery of lysosome.
Elsevier