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Mouse neurotropic recombinants of influenza A viruses

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Summary

Recombinants with known gene constellations between fowl plague virus (FPV) and various prototype influenza virus strains have been examined for neurovirulence in suckling mice. Strongly neurotropic recombinants were obtained from crosses between FPV and the strains virus N, Hong Kong, and PR8, but not between FPV and equi 2 or swine viruses. All highly neurotropic recombinants had RNA segment 4 (HA) derived from FPV and RNA segment 2 (Ptra gene) from the other prototype strain. The derivation of two other RNA segments of the polymerase complex, namely RNA segments 3 (Pol 2) and 5 (NP) and also segment 8 (NS) can modulate these properties. For example, if in recombinants between FPV and virus N in addition to RNA segment 2 also RNA segments 3 and/or 8 are derived from virus N, neurovirulence is further enhanced, while replacement of RNA segment 5 of FPV by the corresponding segment of virus N decreases or abolishes neurovirulence. The derivation of the other genes does not seem to be relevant for neurovirulence in the crosses mentioned above.

Of the prototype strains tested, the turkey England (t. Engl.) strain is the only one which was highly neurotropic for suckling mice. Recombinants between FPV and t. Engl. which have kept the HA gene of t. Engl. were still neurotropic, while those with the HA gene of FPV were completely avirulent.

The results obtained demonstrated that 1. the creation of influenza virus recombinants neurotropic for mice is not a rare event; 2. one of the parents should multiply well in mouse lungs; 3. the presence of a cleavable hemagglutinin is necessary, but not sufficient. In the pair FPV/turkey England the hemagglutinin of turkey England seems to determine neurovirulence.

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References

  1. Appleyard, G., Marber, H. B.: Plaque formation by influenza viruses in the presence of trypsin. J. gen. Virol.25, 351–357 (1974).

    Google Scholar 

  2. Beare, A. S., Hall, T. S.: Recombinant influenza A viruses as live vaccines for man. Lancetii, 1271–1273 (1971).

    Google Scholar 

  3. Bosch, F. X., Orlich, M., Klenk, H.-D., Rott, R.: The structure of the hemagglutinin, a determinant for the pathogenicity of influenza virus. Virology95, 197–207 (1979).

    Google Scholar 

  4. Flehmig, B., Vallbracht, A., Gerth, H.-J.: Influenza virus: association of mouse lung virulence with plaque formation in mouse kidney cells. Intervirol.7, 201–210 (1976).

    Google Scholar 

  5. Ghendon, Y., Klimov, A., Blagoveshenskaya, O., Genkina, D.: Investigation of recombinants of human influenza and fowl plague virus. J. gen. Virol.43, 183–191 (1979).

    Google Scholar 

  6. Haller, O.: A mouse hepatotropic variant of influenza virus. Arch. Virol.49, 99–116 (1975).

    Google Scholar 

  7. Kilbourne, E. D.: Future influenza vaccines and the use of genetic recombinants. Bull. W.H.O.41, 643–651 (1969).

    Google Scholar 

  8. Kilham, L., Oliver, L. S. A.: A latent virus of rats isolated in tissue culture. Virology7, 428–437 (1959).

    Google Scholar 

  9. Mayer, V., Schulman, J. L., Kilbourne, E. D.: Nonlinkage of neurovirulence exclusively to viral hemagglutinin or neuraminidase in genetic recombinants of A/NWS (HON1) influenza virus. J. Virol.11, 272–278 (1973).

    Google Scholar 

  10. Rott, R., Orlich, M., Scholtissek, C.: Attenuation of pathogenicity of fowl plague virus by recombination with other influenza A viruses nonpathogenic for fowl: nonexclusive dependence of pathogenicity on hemagglutinin and neuraminidase of the virus. J. Virol.19, 54–60 (1976).

    Google Scholar 

  11. Rott, R., Scholtissek, C., Klenk, H.-D., Orlich, M.: Structure and pathogenicity of influenza viruses. In:Mahy, B. W. J., Barry, R. D. (eds.), Negative Strand Viruses and the Host Cell, 653–662. London-New York-San Francisco: Academic Press 1978.

    Google Scholar 

  12. Rott, R., Orlich, M., Scholtissek, C.: Correlation of pathogenicity and gene constellation of influenza A viruses. III. Nonpathogenic recombinants derived from highly pathogenic parent strains. J. gen. Virol.44, 471–477 (1979)

    Google Scholar 

  13. Rott, R., Orlich, M., Scholtissek, C.: Differences in the multiplication at elevated temperature of influenza virus recombinants pathogenic and nonpathogenic for chicken. Virology120, 215–224 (1982).

    Google Scholar 

  14. Scholtissek, C.: Influenza virus genetics. Adv. Genetics20, 1–36 (1979).

    Google Scholar 

  15. Scholtissek, C., Harms, E., Rohde, W., Orlich, H., Rott, R.: Correlation between RNA fragments of fowl plague virus and their corresponding gene functions. Virology74, 332–233 (1976).

    Google Scholar 

  16. Scholtissek, C., Rott, R., Orlich, M., Harms, E., Rohde, W.: Correlation of pathogenicity and gene constellation of an influenza A virus (fowl plague). I. Exchange of a single gene. Virology81, 74–80 (1977).

    Google Scholar 

  17. Scholtissek, C., Koennecke, I., Rott, R.: Host range recombinants of fowl plague (influenza A) virus. Virology91, 79–85 (1978).

    Google Scholar 

  18. Scholtissek, C., Vallbracht, A., Flehmig, B., Rott, R.: Correlation of pathogenicity and gene constellation of influenza A viruses. II. Highly neurovirulent recombinants derived from non-neurovirulent or weakly neurovirulent parent virus strains. Virology95, 492–500 (1979).

    Google Scholar 

  19. Scholtissek, C., Spring, S. B.: Extragenic suppression of temperature-sensitive mutations in RNA segment 8 by replacement of different RNA segments with those of other influenza A virus prototype strains. Virology118, 28–34 (1982).

    Google Scholar 

  20. Sugiura, A., Ueda, M.: Neurovirulence of influenza virus in mice. I. Neurovirulence of recombinants between virulent and avirulent strains. Virology101, 440–449 (1980).

    Google Scholar 

  21. Vallbracht, A., Flehmig, B., Gerth, H.-J.: Influenza virus: Appearance of high mouse-neurovirulent recombinants. Intervirol.11, 16–22 (1979).

    Google Scholar 

  22. Vallbracht, A., Scholtissek, C., Flehmig, B., Gerth, H.-J.: Recombination of influenza A strains with fowl plague virus can change pneumotropism for mice to a generalized infection with involvement of the central nervous system. Virology107, 452–460 (1980).

    Google Scholar 

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Bonin, J., Scholtissek, C. Mouse neurotropic recombinants of influenza A viruses. Archives of Virology 75, 255–268 (1983). https://doi.org/10.1007/BF01314891

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