Mouse neurotropic recombinants of influenza A viruses

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Abstract
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.