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
Appleyard, G., Marber, H. B.: Plaque formation by influenza viruses in the presence of trypsin. J. gen. Virol.25, 351–357 (1974).
Beare, A. S., Hall, T. S.: Recombinant influenza A viruses as live vaccines for man. Lancetii, 1271–1273 (1971).
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).
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).
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).
Haller, O.: A mouse hepatotropic variant of influenza virus. Arch. Virol.49, 99–116 (1975).
Kilbourne, E. D.: Future influenza vaccines and the use of genetic recombinants. Bull. W.H.O.41, 643–651 (1969).
Kilham, L., Oliver, L. S. A.: A latent virus of rats isolated in tissue culture. Virology7, 428–437 (1959).
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).
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).
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.
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)
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).
Scholtissek, C.: Influenza virus genetics. Adv. Genetics20, 1–36 (1979).
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).
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).
Scholtissek, C., Koennecke, I., Rott, R.: Host range recombinants of fowl plague (influenza A) virus. Virology91, 79–85 (1978).
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).
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).
Sugiura, A., Ueda, M.: Neurovirulence of influenza virus in mice. I. Neurovirulence of recombinants between virulent and avirulent strains. Virology101, 440–449 (1980).
Vallbracht, A., Flehmig, B., Gerth, H.-J.: Influenza virus: Appearance of high mouse-neurovirulent recombinants. Intervirol.11, 16–22 (1979).
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).
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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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DOI: https://doi.org/10.1007/BF01314891