Tashiro M, Ciborowski P, Reinacher M, Pulverer G, Klenk H D, Rott R
Virology. 1987 Apr;157(2):421-30. doi: 10.1016/0042-6822(87)90284-4.
Several strains of Staphylococcus aureus have been found to secrete proteases that activate infectivity of influenza virus 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 serine 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 intranasally 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 tissue. In contrast, after infection with virus or bacteria alone, there were no significant pathological changes. 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.
已发现几种金黄色葡萄球菌菌株会分泌蛋白酶，这些蛋白酶通过对血凝素进行蛋白水解切割来激活流感病毒的感染性。已对Wood 46和M 86/86这两种细菌菌株的酶进行了较为详细的表征，发现它们是丝氨酸蛋白酶。在底物特异性和抑制剂敏感性方面，它们被证明与胰蛋白酶和纤溶酶相似，但并不相同。单个病毒株的血凝素可被某些葡萄球菌菌株的蛋白酶切割，但不是所有菌株都能切割；并且一种特定的酶只能切割部分而非全部所分析的血凝素。当小鼠经鼻同时感染适当的流感病毒株和金黄色葡萄球菌时，血凝素很容易被激活，从而使病毒在肺中进行多轮复制。在这些条件下，动物会患上致命疾病，肺部组织出现广泛病变。相比之下，单独感染病毒或细菌后，没有明显的病理变化。当葡萄球菌菌株不含能够激活共同感染病毒株血凝素的蛋白酶时，动物不会发病。这些观察结果表明，共同感染的细菌通过提供适合切割激活血凝素的蛋白酶，在流感肺炎的发展中可发挥重要作用。
