It has been proposed that the pathogenicity of the influenza and Sendai vir
us is primarily determined by host cellular proteases that activate viral i
nfectivity, We isolated trypsin-type serine proteases from rat lungs, candi
dates for the processing proteases of viral envelope glycoproteins, such as
tryptase Clara localized in the Clara cells of the bronchial epithelium an
d miniplasmin, These enzymes specifically cleave the precursor of fusion gl
ycoprotein BA of influenza virus at Arg(325), and the F-0 of Sendai virus a
t Arg(116) in the consensus cleavage motif, Gln(Glu)-X-Arg, resulting in th
e induction of infectivity of these viruses. Proteolytic activation of viru
ses by these enzymes occurs extracellularly, probably on the surface and/or
in the lumen of the respiratory tract. On the other hand, we isolated two
compounds from human bronchial lavage, which inhibit the activity of trypta
se Clara. One was a mucus protease inhibitor and the other was a pulmonary
surfactant, These compounds inhibited multiple cycles of virus replication
in vitro and in vivo, but did not themselves affect the hemagglutination an
d the infectivity of the virus. Administration of these compounds in the ai
rway may be useful for preventing and treating infection with influenza vir
us and Sendai virus.