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KMID : 0578319990090030235
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Molecules and Cells
1999 Volume.9 No. 3 p.235 ~ p.244
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Cellular Proteinases Trigger the infectivity of the Influenza A and Sendai Viruses
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Kido, Hiroshi
Murakami, Meiko/Oba, Kumiko/Chen, Ye/Towatari, Takae
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Abstract
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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 serine 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 miniplasmin. These enzymes specifically cleave the precursor of fusion glycoprotein HA of influenza virus at Arg^(325), and the F_(0) of Sendai virus at Arg^(116) 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 respiratory tract. On the other hand, we isolated two compounds from human bronchial lavage, which inhibit 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.
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