Pantropic variant of sendai virus: A mutational change in the proteolytic cleavability of the F glycoprotein alters the organ tropism in mice

Organ tropism of Sendai virus in mice: proteolytic activation of the fusion glycoprotein in mouse organs and budding site at the bronchial epithelium

“…In general, the epithelial, mesothelial, and vascular endothelial cells were predominantly involved. This is consistent with the finding with F1-R infection in vivo (38,39). With wild-type virus, however, the results were quite different from infections in vivo, in which viral antigens were detected exclusively in the respiratory epithelium (36).…”

“…On the other hand, the F protein of F1-R was cleaved in the organs as indicated by F1 and F2; some uncleaved F protein was detected. The differences in the migration of F protein bands Fo and F2 are consistent with the finding that the F2 subunit of F1-R is lacking in a carbohydrate side chain (38,39). Confirmation of the phenotype of the M protein of F1-R, with a faster-migrating band, is also evident (38).…”

“…The mutant was found to be pantropic in mice. Infectious virus was produced and multiple cycles of replication ensued in many organs in addition to the lung (38,39). These results, taken together with similar observations with virulent and avirulent strains of Newcastle disease virus (23,24,40) and avian influenza viruses (2,3,(13)(14)(15), suggest that the structural change in the F glycoprotein of F1-R, with enhanced cleavability, resulted in the broad host range in mice (38,39).…”

“…Posttranslational cleavage of the fusion (F) glycoprotein into F, and F2 subunits is a prerequisite for the virus to express infectivity (7,8,28,29). Therefore, the host range and organ tropism of Sendai virus have been proposed to be primarily attributed to the presence of an activating protease(s) in target tissues and the susceptibility of F protein to the protease(s) (5,10,15,23,36,39). The cleavage site of F protein contains a single arginine residue.…”

“…Infectious virus was produced and multiple cycles of replication ensued in many organs in addition to the lung (38,39). These results, taken together with similar observations with virulent and avirulent strains of Newcastle disease virus (23,24,40) and avian influenza viruses (2,3,(13)(14)(15), suggest that the structural change in the F glycoprotein of F1-R, with enhanced cleavability, resulted in the broad host range in mice (38,39). Two questions, however, remain to be answered: (i) whether mouse organs other than the respiratory tract are susceptible to wild-type virus but permissive for F1-R; and (ii) whether the activating protease(s) for wild-type F protein is present only in the respiratory organs, whereas the proteases for F1-R are distributed in the systemic organs.…”