Zhirnov O P, Ovcharenko A V, Bukrinskaia A G
Vopr Virusol. 1981 Nov-Dec(6):677-87.
The effect of chicken, canine, and porcine plasm containing plasmin proenzyme, plasminogen, on influenza virus hemagglutinin produced in homologous and heterologous tissue cells was studied. The cells incubated with the homologous plasm were found to produce virions containing both cleaved and uncleaved hemagglutinin whereas the cells incubated without plasm or with heterologous plasm produced virions with uncleaved hemagglutinin. The infectious activity of the virus produced by cells with the homologous plasm was much higher than that of the virus grown without the latter or with heterologous plasm. The addition to the culture medium of plasminogen inhibitors together with plasm eliminated the proteolytic effect of the plasm on virion hemagglutinins resulting in the production of virions with uncleaved hemagglutinin and low infectious activity. In vivo, in experimental influenza infection of mice and chickens, highly infectious virus with cleaved hemagglutinin was isolated from the organs of the animals. The organs of the animals inoculated with inhibitors of proteolytic enzymes yielded virus of low infectivity with uncleaved hemagglutinin. Administration of proteases inhibitors to the infected animals prevented the spread of virus infection in animals and had a therapeutic effect. The experimental data suggest that activation of virions with proteolytic enzymes of the host, in particular, plasmin by means of hemagglutinin cleavage is the key mechanism in the development and spread of influenza infection in the host.
研究了含有纤溶酶原(血浆酶原)的鸡、犬和猪血浆对同源和异源组织细胞中产生的流感病毒血凝素的影响。发现与同源血浆一起孵育的细胞产生的病毒粒子同时含有裂解和未裂解的血凝素,而未与血浆或与异源血浆一起孵育的细胞产生的病毒粒子含有未裂解的血凝素。含有同源血浆的细胞产生的病毒的感染活性远高于不含有血浆或含有异源血浆培养所产生病毒的感染活性。在培养基中加入纤溶酶原抑制剂和血浆,消除了血浆对病毒粒子血凝素的蛋白水解作用,导致产生含有未裂解血凝素且感染活性低的病毒粒子。在体内,在小鼠和鸡的实验性流感感染中,从动物器官中分离出具有裂解血凝素的高传染性病毒。接种蛋白水解酶抑制剂的动物器官产生的病毒感染性低,且血凝素未裂解。给感染动物施用蛋白酶抑制剂可防止病毒感染在动物体内传播,并具有治疗作用。实验数据表明,宿主的蛋白水解酶,特别是通过血凝素裂解激活纤溶酶,是流感感染在宿主体内发生和传播的关键机制。