Characterization of a pantropic variant of Sendai virus derived from a host range mutant.

A variant (F1-R) was isolated from a temperature-sensitive host range mutant (ts-f1) of Sendai virus. F1-R was no longer temperature-sensitive but it retained the host range phenotype. Unlike wild-type virus, F1-R and ts-f1 undergo multiple cycles of replication in several cell lines in the absence of trypsin. This was attributed to proteolytic activation of the fusion (F) glycoprotein of the host range mutants, in cell nonpermissive to wild-type virus. In mice infected intranasally the variant F1-R caused a generalized infection. This was shown by immunohistology and with infectious virus being recovered from several organs whereas infection with wild-type virus was restricted to the lung. These observations indicate that the pantropic property of F1-R is the result of proteolytic activation of the virus by ubiquitous proteases. Nucleotide sequence analyses revealed that ts-f1 and F1-R differed from the wild-type virus by mutations at the region of the cleavage site of F and at the glycosylation site of the F2 subunit. The findings indicated that these mutations are responsible for the increased cleavability of the F protein of ts-f1 and F1-R and therefore are important determinants for the pantropism of F1-R.