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“类胰蛋白酶Clara”，存在于大鼠支气管上皮细胞的Clara细胞中并由其分泌。类胰蛋白酶Clara通过蛋白水解作用裂解大鼠肺中的F蛋白，激活仙台病毒子代，从而促进病毒复制和肺病理学的多个循环.仙台病毒在支气管上皮细胞（感染的主要靶细胞）上的出芽极性被证明决定了器官嗜性。野生型病毒的顶端出芽是导致气道内局部感染的原因，而基底外侧出芽是子代病毒向远处器官全身传播导致全身感染所必需的。除了F蛋白的蛋白水解活化外，基底外侧病毒糖蛋白的表达也是诱导细胞融合的先决条件.突变仙台病毒，F1-R，芽双极在上皮细胞中，被证明破坏微管网络感染的细胞，导致受损的细胞极性。通过对野生型和F1-R病毒的全序列的比较分析，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.