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Influenza virus infection of newborn rats: virulence of recombinant strains prepared from influenza virus strain A/Okuda/57.

Infant rats were infected intranasally with wild influenza virus strains, attenuated strain A/Okuda/57 or recombinants prepared from these parents. The growth of viruses in the turbinates or lungs, and the ability of virus infections to potentiate subsequent bacterial infection by Haemophilus influenzae (HIb) were measured. The two wild strains of virus and a recombinant strain WRL105, known to be virulent for man, reached titres of 10(5.1)--10(6.5) EBID50/ml in the turbinates of infant rats 48 h after infections; infection by these viruses was followed by HIb bacteraemia in 77--92% and meningitis in 58--75% of animals. In contrast, virus strains known to be attenuated for man grew to lower titres in infant-rat turbinates and promoted a lower incidence of systemic infection by HIb than the virulent strains. A comparison of the various results of infection of infant rats with influenza virus strains of known pathogenicity for man indicated that the subsequent incidence of HIb bacteraemia was the most discriminating measurement of virus virulence; the range of yields of attenuated virus in rat turbinates overlapped that of virulent strains. These results, together with those of previous studies, indicate that the behaviour of influenza viruses in infant rats is an indication of virus virulence for man, and could provide a test of virulence that would facilitate the development of live attenuated virus vaccines for human use.