ROLE OF VIRION M2 PROTEIN IN INFLUENZA-VIRUS UNCOATING - SPECIFIC REDUCTION IN THE RATE OF MEMBRANE-FUSION BETWEEN VIRUS AND LIPOSOMES BY AMANTADINE

The anti-influenza virus drug amantadine was shown to reduce the rate of fusion of liposomes with influenza A viruses whose replication is i nhibited by this drug. The fusion with amantadine-resistant viruses wa s unaffected. Experiments with reassortant and mutant viruses showed t hat this effect was linked to the M2 protein and not to the haemagglut inin of the virus. The proton ionophore monensin, on the other hand, s ubstantially increased the rate of fusion of the viruses tested. These results indicate that the kinetics of virus-liposome fusion can be mo dulated by the virus M2 protein, the target of amantadine action, and it is postulated that the M2 ion channel functions by transporting pro tons into the virion interior and facilitating virus uncoating.