Enzymes and inhibitors in airway that regulate infection of influenza virus
Murakami, Meiko The University of Tokushima
Towatari, Takae The University of Tokushima
Ohba, Kumiko The University of Tokushima
Kido, Hiroshi The University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
mucus protease inhibitor (MPI)
It has been proposed that the pathogenicity of the influenza and Sendai virus is primarily determined by host cellular proteases that activate viral infectivity. We isolated trypsin-type serin proteases from rat lungs, candidates for the processing proteases of viral envelope glycoproteins, such as tryptase Clara localized in the Clara cells of the bronchial epithelium and mini-plasmin. These enzymes specifically cleave the precursor of fusion glycoprotein HA of influenza virus at Arg325, and the Fo of Sendai virus at Arg116 in the consensus cleavage motif, Gln(Glu)-X-Arg, resulting in the induction of infectivity of these viruses. Proteolytic activation of viruses by these enzymes occurs extracellularly, probably on the surface and/or in the lumen of the respiratory tract. On the other hand, we isolated two compounds from human bronchial lavage, which inhibitor the activity of tryptase Clara. One was a mucus protease inhibitor and the other was a pulmonary surfactant.
These compounds inhibited multiple cycles of virus replication in vitro and in vivo, but did not themselves affect the hemagglutination and the infectivity of the virus. Administration of these compounds in the airway may be useful for preventing and treating infection with influenza virus and Sendai virus.
Shikoku Acta Medica
sam_55_5_174.PDF 4.56 MB
Institute of Advanced Medical Sciences