Identification of Determinants for Tropism of Sendai virus

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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.