Identification of Determinants for Tropism of Sendai virus

1.我们分离并鉴定了一种新的丝氨酸蛋白酶，命名为“Tryptase Clara”，存在于大鼠支气管上皮Clara细胞中并由其分泌。结论：1.类胰蛋白酶Clara可通过蛋白水解性裂解大鼠肺组织中的F蛋白激活仙台病毒后代，从而促进病毒复制和肺病理的多个循环。仙台病毒在呼吸道上皮细胞的萌发极性决定了器官的嗜性，支气管上皮细胞是感染的主要目标。野生型病毒的顶端萌发是呼吸道特许感染的原因，而基侧萌发是子代病毒系统性传播到远处器官导致全身感染所必需的。除了F蛋白的蛋白水解性激活外，病毒糖蛋白的碱侧表达是诱导细胞融合的先决条件。突变的仙台病毒F1-R在上皮细胞中以双极方式萌发，被证明破坏了感染细胞中的微管网络，导致细胞极性受损。通过对野生型病毒和F1-R病毒全核苷酸序列的比较分析，认为突变的M蛋白是造成这一现象的原因。

1. We isolated and characterized a novel serine-protease designated "Tryptase Clara", present in and secreted from the Clara cells of rat bronchial epithelia. Tryptase Clara was revealed to activate Sendai virus progeny by proteolytic cleavage of the F protein in rat lungs, and thereby facilitate multiple cycles of viral replication and pneumopathology.2. Budding polarity of Sendai virus at the bronchial epithelial cells, the primary target of infection, was shown to determine the organ tropism. Apical budding by wild-type virus is responsible for licalized infection in the airways, whereas basolateral budding is required for systemic spread of progeny virus to distant organs resulting in a systemic infection.3. In addition to proteolytic activation of the F protein, basolateral expression of viral glycoproteins is a prerequisite for inducing cell fusion.4. A mutant Sendai virus, F1-R, which buds bipolarly in epithelial cells, was shown to disrupt microtubule network in infected cells, resulting in impaired cellular polarity. By comparative analysis of the entire nucleotide sequence of wild-type and F1-R viruses, the mutated M protein was suggested to be responsible for this phenomenon.