Altered budding site of a pantropic mutant of Sendai virus, F1-R, in polarized epithelial cells.

A protease activation mutant of Sendai virus, F1-R, causes a systemic infection in mice, whereas wild-type virus is exclusively pneumotropic (M. Tashiro, E. Pritzer, M. A. Khoshnan, M. Yamakawa, K. Kuroda, H.-D. Klenk, R. Rott, and J. T. Seto, Virology 165:577-583, 1988). Budding of F1-R has been observed bidirectionally at the apical and basolateral surfaces of the bronchial epithelium of mice and of MDCK cells, whereas wild-type virus buds apically (M. Tashiro, M. Yamakawa, K. Tobita, H.-D. Klenk, R. Rott, and J. T. Seto, J. Virol. 64:3627-3634, 1990). In this study, wild-type virus was shown to be produced primarily from the apical site of polarized MDCK cells grown on permeable membrane filters. Surface immunofluorescence and immunoprecipitation analyses revealed that transmembrane glycoproteins HN and F were expressed predominantly at the apical domain of the plasma membrane. On the other hand, infectious progeny of F1-R was released from the apical and basolateral surfaces, and HN and F were expressed at both regions of the cells. Since F1-R has amino acid substitutions in F and M proteins but none in HN, the altered budding of the virus and transport of the envelope glycoproteins might be attributed to interactions by F and M proteins. These findings suggest that in addition to proteolytic activation of the F glycoprotein, the differential site of budding, at the primary target of infection, is a determinant for organ tropism of Sendai virus in mice.