Proteolytic activation of influenza WSN virus in cultured cells is performed by homologous plasma enzymes.

The effect of chick embryo allantoic fluid, porcine plasma or canine plasma on virus progeny was studied in cultured chicken, porcine and canine cells infected with influenza WSN virus. Cells incubated either without plasma or with heterologous plasma produced virions which had uncleaved haemagglutinin and low infectivity. Cells incubated with homologous plasma produced highly infectious virions with cleaved haemagglutinin. Little increase of progeny virus infectivity was observed in canine cell-porcine plasma and porcine cell-canine plasma host systems. The addition of protease inhibitors to culture containing homologous plasma, in particular epsilon-amino-n-caproic acid (an inhibitor of plasminogen activation), suppressed cleavage of haemagglutinin, and virions which had uncleaved haemagglutinin and low infectivity were produced by the cells. It therefore follows that haemagglutinin cleavage and activation of influenza WSN virus infectivity in cultured cells is most efficiently performed by homologous plasma proteolytic enzyme(s). The mechanism of selective plasma-mediated influenza virus proteolytic activation in homologous cells is discussed.