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Suppression of Influenza Virus Replication in Infected Mice by Protease Inhibitors

The D.I. Ivanovsky Institute of Virology, Moscow, U.S.S.R.

Administration of the protease inhibitors, -aminocaproic acid or aprotinins, to mice infected with mouse-adapted influenza virus strain A/PR/8/34 (H0N1) and A/Aichi/2/68 (H3N2) reduced virus replication in the lungs. Up to 100-fold reduction of virus titre and virus-induced neuraminidase activity were revealed in mouse lungs under protease inhibitor treatment. As a result, drug-treated mice rapidly cleared the virus from their lungs. The predominant synthesis was of non-infectious virions with uncleaved haemagglutinin in the lungs of drug-treated mice, in contrast to the production of highly infectious virions with proteolytically cleaved haemagglutinin in untreated mice. These observations suggest that protease inhibitors suppress influenza virus replication in mouse lungs due to prevention of haemagglutinin cleavage and virus proteolytic activation.

Keywords: influenza virus, infection, antiviral compounds, protease inhibitors

Received 27 June 1983; accepted 20 September 1983.

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