Martin Vey

Hemagglutinin activation of pathogenic avian influenza viruses of serotype H7 requires the protease recognition motif R-X-K/R-R

Abstract The hemagglutinin of influenza virus A/FPV/Rostock/34 (H7) was altered at its multibasic cleavage site by site-directed mutagenesis and assayed for proteolytic activation after expression in CV-1 cells. The results indicated that the cellular protease responsible for activation recognizes the tetrapeptide motif R-X-K/R-R that must be presented in the correct sequence position. Studies on plaque variants of influenza virus A/fowINictoria/75 (H7N7) showed that alteration of the consensus sequence resulted in a loss of pathogenicity for chickens.

Proteolytic Activation of Influenza Viruses: Substrates and Proteases

Like many other viral glycoproteins, the hemagglutinin (HA) of influenza viruses is activated by proteolytic cleavage. Cleavage which is necessary for the fusion activity of the hemagglutinin and thus for the infectivity of the virus is exerted by host cell proteases, and the presence of an appropriate enzyme determines whether infectious virus is made in a given cell. Proteolytic activation is therefore indispensable for effective virus spread in the infected host and has been found to be a prime determinant for virus pathogenicity. This concept has been derived mainly from studies on avian influenza viruses. The pathogenic strains of these viruses are activated by ubiquitous proteases and cause therefore systemic infection mostly leading to rapid death of the animal, whereas activation of the apathogenic strains occurs only in epithelial cells of the respiratory or the enteric tract resulting in local infection of these organs. The mammalian influenza viruses, including the human ones, resemble the apathogenic avian strains in possessing also hemagglutinins of restricted cleavability and in causing usually local infection of the respiratory tract.1