We examined the effect of a serratial
exoprotease on the pathogenesis of influenza virus
infection in mice as a model of complicated respiratory
infection by bacteria and virus in humans. The 56-kilodalton (56-kDa)
protease from Serratia marcescens was administrated intranasally to mice at a dose of 10, 20, or 40 micrograms from day 0 to day 3 after inoculation of the influenza virus. Administration of the
protease resulted in remarkable enhancement of the lethal effect of the virus and enhancement of pathological changes in the lungs. Influenza virus replication, determined by plaque-forming assay, was accelerated by the
protease. Namely, we found a 100-fold increase in virus yield by day 2. The 56-kDa
protease caused generation of
plasmin activity in the lungs. In vitro experiments showed that
plasmin greatly enhanced the yield of influenza virus, although the effect of the 56-kDa
protease by itself was much lower than that of
plasmin. Furthermore, the 56-kDa
protease could induce
plasmin production indirectly via activation of
plasminogen by the
Hageman factor-dependent cascade in the in vitro system. We conclude that this major serratial
exoprotease has a deleterious effect on mice infected with influenza virus and that this effect seems to result from enhancement of viral growth by indirect acceleration of
plasmin generation induced by the
protease.