Nonlinkage of neurovirulence exclusively to viral hemagglutinin or neuraminidase in genetic recombinants of A-NWS (HON1) influenza virus.

Genetic recombination of the neurovirulent A/NWS/cc-p (H0N1) and the non-neurovirulent A/Jap.305/57 (H2N2) influenza viruses in which hemagglutinin and neuraminidase were segregated (H0N2, H2N1) were studied for neurovirulence in mice immunosuppressed with cyclophosphamide (CPA) which permitted full expression of virulence. Both H0N2 and H2N1 recombinants replicated in the brain (in contrast to the H2N2 parent) and both produced lethal effects in CPA-treated animals. Therefore we conclude that A/NWS (H0N1) neurovirulence is not exclusively linked with either the hemagglutinin or the neuraminidase of the virus. The H0N2 and H2N1 recombinants have revealed the existence of two separate attributes of neurovirulence: (i) the capacity of virus to initiate intracerebral infection and (ii) the capacity of infection, once initiated, to produce lethal disease. These studies provide further evidence for the polygenic nature of A/NWS neurovirulence.