Proteolytic cleavage of the hemagglutinin polypeptide of influenza virus. Function of the uncleaved polypeptide HA.

Abstract

Abstract The cleavage of the HA polypeptide, the largest glycoprotein of influenza virus, to polypeptides HA1 and HA2 has been studied using the WSN strain of influenza A 0 and the RI/5 − strain of influenza A 2 grown in different host cells. Cleavage of the HA polypeptide is not required for the assembly of infectious, hemagglutinating virions. Cleavage is both strain dependent and host cell dependent, and correlates with the extent of cell damage, suggesting that the enzymes involved are host cell specified. Virions grown in MDBK cells without calf serum in the medium contain almost entirely uncleaved HA polypeptides. Virions harvested early in the growth cycle contain more uncleaved HA polypeptide than virions harvested late from the same cells when cytopathic effects are extensive. The proteolytic nature of the cleavage has been demonstrated in vitro with trypsin. Comparison of the specific hemagglutinating activity and infectivity of virions which contain different amounts of the uncleaved HA polypeptide and the cleavage products HA1 and HA2, and of the capacity of such virions to react with the soluble glycoprotein receptor substance fetuin, have shown that uncleaved HA polypeptides are as active in hemagglutination and adsorption to cellular and soluble receptors as are the disulfide-bonded complexes composed of HA1 plus HA2. The proteolytic cleavage of the HA polypeptide to HA1 and HA2 is thus not required for virus assembly or for full expression of the biological properties of the virion. Rather, it appears to be a nonessential result of events occurring in infected cells which are undergoing cytopathic effects.