インフルエンザウイルスの感染感受性を決定する生体内因子群とその作用機序からみる新たな治療・予防への展開

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  • Host cellular factors, which determine the susceptibility of influenza virus infection : the application of antiviral compounds to prevention and treatment.
  • インフルエンザ ウイルス ノ カンセン カンジュセイ オ ケッテイスル セイタイナイ インシグン ト ソノ サヨウ キジョ カラ ミル アラタナ チリョウ ヨボウ エノ テンカイ

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Extracellular cleavage of virus envelope fusion glycoprotein, hemagglutinin, by host cellular proteases is a prerequisite for the infectivity of mammalian and nonpathogenic avian influenza viruses. In search of such target processing proteases in the airway, we found ectopic anionic trypsin I, tryptase Clara and mini-plasmin. Interestingly, these processing enzymes were localized in the air way with different distribution. In addition, these enzymes showed the different sensitivities to various strains of influenza A viruses. These findings suggested that host cellular proteases determine the susceptibility of influenza virus infection. On the other hand, the activity of these enzymes is strictly regulated by endogenous inhibitory compounds such as mucas protease inhibitor in the upper respiratory tract and pulmonary surfactant in the lower respiratory tract. Furthermore, we identified that ambroxol, known as a mucolytic agent, stimulate the suppressors of influenza-virus proliferation, such as mucas protease inhibitor, pulmonary surfactant and IgA. These findings suggested that the concentration of suppressors in the airway fluid significantly affect the pathogenicity of influenza virus infection. In this review, we discussed that the effects of antiviral compounds including ambroxol on prevention and treatment of influenza virus infection.

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