Aminoadamantane-resistant strains of influenza A2 virus.

After one passage of influenza A2/Singapore/1/57 virus in mice treated with 150 mg./kg./day of aminoadamantane, a partially drug-resistant strain of virus was detected in 1 of 12 mice. The isolation rate of aminoadamantane-resistant viruses increased to 8 after three passages in drug-treated mice. Some virus strains showed a 500-fold increase in resistance to aminoadamantane and to the structurally related compounds alpha-methyl-1-adamantane methylamine and 2-adamantanamine sulphate. No aminoadamantane-resistant viruses were detected after passage of influenza four times in mice treated with lower (15 or 1.5 mg./kg./day) concentrations of aminoadamantane. Aminoadamantane had no detectable effect on the development of lung lesions in mice infected with the drug-resistant influenza strain, whereas lung lesions were reduced in aminoadamantane treated mice infected with a control strain of influenza A2/Singapore virus. No differences were detected in the buoyant density in caesium chloride, morphology or serology between control and aminoadamantane-resistant strains of virus. These drug-resistant influenza viruses may be useful for detailed studies of the mode of action of aminoadamantane.