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  • Title: [Rapid method of producing influenza A virus variants resistant to amantadine and remantadine and their primary characteristics].
    Author: Vladyko AS, Shobukhov VM, Linitskaia GL, Galegov GA.
    Journal: Vopr Virusol; 1982; 27(4):426-32. PubMed ID: 7135921.
    Abstract:
    A rapid method for production of influenza A virus variants resistant to the adamantane series derivatives, amantadine and remantadine, has been developed. The method consisted of two stages. In the first, the virus was subjected to one passage in the presence of the preparations under a liquid overlayer in a one-cycle experiment. In the second stage, the resulting virus was titrated by the plaque method, the agar overlay containing the preparations in a concentration which was not toxic for the cells. Production of large and small plaques in the presence of the preparations in agar was an indication for selection of resistant virus variants and their further study. Cross-resistance of amantadine- and remantadine-resistant variants to remantadine and amantadine, respectively, was studied. No complete cross-resistance in these viruses could be demonstrated. The amantadine-resistant virus was not inhibited by remantadine, whereas the remantadine-resistant virus was significantly inhibited by amantadine as was demonstrated by both virological methods and by induction of RNA-dependent RNA polymerase and synthesis of viral proteins. The experimental results suggest that the mechanisms of formation of influenza A virus resistance to amantadine and remantadine are not absolutely identical.
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