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Relation between drug resistance and antigenicity among norakin-resistant mutants of influenza A (fowl plague) virus

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Summary

Norakin-resistant (NR) mutants of fowl plague virus (A/FPV/Wey-bridge, H7N7) have 1 to 2 (in one instance 3) amino acid substitutions in different positions of the heavy (HA 1) and/or light (HA 2) subunits of the haemagglutinin (HA) molecule. Investigation of NR mutants using the haemagglutination inhibition test with monoclonal antibodies (MAb) to the HA of A/seal/Massachusetts/80 (H7N7) virus revealed that one of the mutants (NR 1) differs antigenically from the wild-type fowl plague virus: its haemagglutination was not inhibited by MAb 55/2 and 58/6. By contrast, MAb-resistant (escape) mutants, selected from the wild-type fowl plague virus under pressure from MAb 55/2 or 58/6, showed reduced drug sensitivity. These findings suggest a possibility of correlation between alteration of influenza virus antigenicity and change of its sensitivity to drugs whose target is the haemagglutinin. This potential effect should be taken into account when antiviral substances directed to surface influenza virus antigens are being developed for use as antiviral drugs.

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References

  1. Air GM (1979) Nucleotide sequence coding for the “signal peptide” and N terminus of the haemagglutinin from an asian (H2N2) strain of influenza virus. Virology 97: 468–472

    Google Scholar 

  2. Appleyard G (1977) Amantadine-resistance as a genetic marker for influenza viruses. J Gen Virol 36: 249–255

    Google Scholar 

  3. Bean WJ, Threlkeld SC, Webster RG (1989) Biological potential of amantadine-resistant influenza A virus in an avian model. J Infect Dis 159: 1050–1056

    Google Scholar 

  4. Belshe RB, Hall-Smith MH, Hall CB, Betts R, Hay AJ (1988) Genetic basis of resistance to rimantadine emerging during treatment of influenza virus infection. J Virol 62: 1508–1512

    Google Scholar 

  5. Belshe RB, Burk B, Newman F, Cerruti RL, Sim IS (1989) Resistance of influenza A virus to amantadine and rimantadine: results of one decade of surveillance. J Infect Dis 159: 430–435

    Google Scholar 

  6. Brown LE, Murray JM, White DO, Jackson DC (1990) An analysis of the properties of monoclonal antibodies directed to epitopes of influenza virus haemagglutinin. Arch Virol 114: 1–26

    Google Scholar 

  7. Daniels RS, Downie JC, Hay AJ, Knossow M, Skehel JJ, Wang ML, Wiley DC (1985) Fusion mutants of the influenza virus haemagglutinin glycoprotein. Cell 40: 431–439

    Google Scholar 

  8. Ghendon Y, Markushin S, Heider H, Melnikov S, Lotte V (1986) Haemagglutinin of influenza A virus is a target for antiviral effect of Norakin. J Gen Virol 67: 1115–1122

    Google Scholar 

  9. Hay AJ, Wolstenholme AJ, Skehel JJ, Smith MH (1985) The molecular basis of the specific anti-influenza action of amantadine. EMBO J 4: 3021–3024

    Google Scholar 

  10. Hay AJ, Zambon MC, Wolstenholme AJ, Skehel JJ, Smith MH (1986) Molecular basis of resistance of influenza A viruses to amantadine. J Antimicrob Chemotherapy 18 [Suppl B]: 19–29

    Google Scholar 

  11. Hayden FG, Belshe RB, Clover RD, Hay AJ, Oakes MG, Soo W (1989) Emergence and apparent transmission of rimantadine-resistant influenza A virus in families. N Engl J Med 321: 1696–1702

    Google Scholar 

  12. Heider H, Adamczyk B, Presber HW, Schröeder C, Feldblum R, Indulen MK (1981) Occurrence of amantadine- and rimantadine-resistant influenza A virus strains during the 1980 epidemic. Acta Virol (Praha) 25: 395–400

    Google Scholar 

  13. Heider H, Markushin S, Schröeder C, Ghendon Y (1985) The influence of Norakin on the reproduction of influenza A and B viruses. Arch Virol 86: 283–290

    Google Scholar 

  14. Kida H, Brown RE, Webster RG (1982) Biological activity of monoclonal antibodies to operationally defined antigenic regions of the haemagglutinin molecule of A/seal/Massachusetts/1/80 (H7N7) influenza virus. Virology 122: 38–47

    Google Scholar 

  15. Klimov AI, Prösch S, Schäfer J (1992) Subtype H7N7 influenza viruses: comparative antigenic and molecular analysis of the HA-, M-, and NS-genes. Arch Virol 122: 143–161

    Google Scholar 

  16. Oxford JS, Logan IS, Potter CW (1970) In vivo selection of an influenza A 2 strain resistant to amantadine. Nature 226: 82–83

    Google Scholar 

  17. Pemberton RM, Jennings R, Porter CW, Oxford JS (1986) Amantadine resistance in clinical influenza A (H3N2) and (H1N1) virus isolates. J Antimicrob Chemother 18 [Suppl B]: 135–140

    Google Scholar 

  18. Prösch S, Heider H, Schröeder C, Krüger DH (1988) Mutations in the haemagglutinin gene associated with influenza virus resistance to norakin. Arch Virol 102: 125–129

    Google Scholar 

  19. Prösch S, Heider H, Schröeder C, Shilov AA, Sinitzyn BV, Blinov BM, Krüger DH, Frommel C (1990) Mapping mutations in influenza A virus resistant to norakin. FEBS Lett 267: 19–21

    Google Scholar 

  20. Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467

    Google Scholar 

  21. Schröeder C, Heider H, Hegenscheid B, Schöffel M, Bubovich VI, Rosenthal HA (1985) The anticholinergic anti-Parkinson drug Norakin selectively inhibits influenza virus replication. Antiviral Res [Suppl] 1: 95–99

    Google Scholar 

  22. Skehel JJ, Bayley PM, Brown EB, Martin SR, Waterfield MD, White JM, Wilson IA, Wiley DC (1982) Changes in the conformation of influenza virus haemagglutinin at the pH optimum of virus-mediated membrane fusion. Proc Natl Acad Sci USA 79: 968–972

    Google Scholar 

  23. Webster RG, Kawaoka Y, Bean WJ, Beard CW, Brugh M (1985) Chemotherapy and vaccination: a possible strategy for the control of highly virulent influenza virus. J Virol 55: 173–176

    Google Scholar 

  24. Wiley DC, Skehel JJ (1987) The structure and function of the haemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem 56: 365–394

    Google Scholar 

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Klimov, A.I., Markushin, S.G., Prösch, S. et al. Relation between drug resistance and antigenicity among norakin-resistant mutants of influenza A (fowl plague) virus. Archives of Virology 124, 147–155 (1992). https://doi.org/10.1007/BF01314632

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  • DOI: https://doi.org/10.1007/BF01314632

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