Protection of mice from wild-type Sendai virus infection by a trypsin-resistant mutant, TR-2

Abstract

A trypsin-resistant mutant of Sendai virus, TR-2, which could be activated by chymotrypsin but not by trypsin or the protease present in mouse lung, was inoculated intranasally into mice after being activated in vitro. TR-2 hardly brought about clinical illness or lung lesions in mice; the protease present in the lung could not activate the progeny virus, and the infection terminated after one-step replication. Nevertheless, the immunoglobulin A antibody against wild-type Sendai virus was produced in the respiratory tracts as well as the serum immunoglobulin G antibody, and the mice were protected from the challenge of the wild-type Sendai virus. On the basis of these results, TR-2 may provide a new model of live vaccine for paramyxoviruses; its availability as a live vaccine is also discussed.

Initiation of Sendai virus multiplication from transfected cDNA or RNA with negative or positive sense

“…The presence of the trypsin-like enzyme, tryptase Clara, is a critical precondition for the wild-type SeV to spread and cause pneumonia in the lungs of rats and probably mice-the natural hosts (Tashiro et al 1993). Thus, the mutant TR-5 cannot spread sufficiently in the lung to produce the disease but it can induce protective immunity in mice, and can therefore be used as an attenuated live vaccine (Tashiro & Homma 1985).…”

Pneumopathogenicity of a Sendai virus protease-activation mutant, TCs, which is sensitive to trypsin and chymotrypsin

“…Since envelope fusion activity of F protein is acquired by posttranslational cleavage by certain proteases inherent to host cells (3,14,15,(20)(21)(22)(23), the structure of F protein around the cleavage site is thought to be important for the virus to express infectivity and to determine host range and organ tropism. This view was verified by the fact that the wild-type virus whose F protein accepted the cleavage by trypsin next to arginine at residue 116 could multiply in the lungs of mice (24) in which trypsin like protease was present (23), while trypsin-resistant mutants TR-2 and TR-5 could not multiply because the arginine residue mutated to isoleucine and were not activated by the proteases in the lungs of mice (24,25). The following report by Tashiro et al (26) also supports the above-described view: a variant (F1-R) of Sendai virus which exhibited susceptibility to the activation by ubiquitous proteases as a result of the amino acid substitutions around the cleavage site and/or at the glycosylation site of the F2 subunit caused a systemic infection in mice.…”

Virus Activation by Host Proteinases. A Pivotal Role in the Spread of Infection, Tissue Tropism and Pathogenicity

“…Human influenza A virus is similar to murine Sendai virus in that both possess a single-arginine motif and target the respiratory tract. In view of the potential as a live vaccine of proteinase-activation mutants of Sendai virus that have a cleavage site susceptible to enzymes other than arginine-specific enzymes (50), it would be worth engineering similar mutants of influenza virus. VAPs undoubtedly are not solely involved in virus activation.…”