Fundamental researches on the pathogenesis and therapy of influenza virus pneumonia

1.已经发现金黄色葡萄球菌的几种菌株分泌蛋白酶，所述蛋白酶通过血凝素的蛋白水解裂解来激活甲型流感病毒的感染性。细菌菌株wood 46和M/86/86的酶已经被详细地表征，并且被发现是sekine蛋白酶。在其底物特异性和抑制剂的敏感性，他们被证明是类似的，但不相同的胰蛋白酶和纤溶酶。单个病毒株的血凝素可以被一些但不是所有葡萄球菌株的蛋白酶切割，并且给定的酶只能切割一些但不是所有分析的血凝素。当小鼠同时感染流感病毒和S.在金黄色葡萄球菌感染后，血凝素容易被激活，从而允许病毒在肺中进行多个循环复制。在这些条件下，动物患上了致命的疾病，在肺组织中表现出广泛的病变。而单纯感染病毒或细菌后，则无明显病理改变。当葡萄球菌菌株不包含能够激活共感染病毒菌株的血凝素的蛋白酶时，动物没有表现出疾病。这些观察结果表明，共感染细菌可以通过提供适合于血凝素裂解激活的蛋白酶在流感肺炎的发展中发挥重要作用。蛋白酶抑制剂亮抑酶肽可阻止葡萄球菌蛋白酶介导的流感病毒（A/swine/1976/31）的多步复制。它还抑制病毒复制和致命性肺炎的发展，在小鼠与病毒和金黄色葡萄球菌共感染。

1. Several strains of Staphylococcus aureus have been found to secrete proteases that activate infectivity of influenza A viruses by proteolytic cleavage of the hemagglutinin. The enzymes of the bacterial strains wood 46 and M/86/86 have been characterized in some detail and were found to be sekine proteases. In their substrate specificities and inhibitor sensitivities they proved to be similar to, but not identical with trypsin and plasmin. The hemagglutinin of an individual virus strain could be cleaved by the proteases of some but not all staphylococcal strains, and a given enzyme could cleave only some but not all hemagglutinins analyzed. When mice were coinfected with the appropriate strains of influenza virus and S. aureus, the hemagglutinin was readily activated allowing multiple cycles of virus replication in the lung. Under these conditions, the animals came down with a fatal disease exhibiting extended lesions in the lung tissues. In contrast, after infection with virus or bacteria alone, there were no significant pathological changed. When the Staphylococcal strain did not contain a protease that was able to activate the hemagglutinin of the coinfecting virus strain, the animals did not exhibit disease. These observations demonstrate that coinfecting bacteria can play an essential role in the development of influenza pneumonia by providing a protease suitable for cleavage activation of the hemagglutinin.2. The protease inhibitor, leupeptin, prevented multiple step replication of an influenza virus (A/swine/1976/31) mediated by staphylococcal proteases. It also suppressed virus replication and development of fatal pneumonia in mice coinfected with the virus and staphylococcus aureus.