In vivo and in vitro hamster models in the assessment of virulence of recombinant influenza viruses

Abstract

The virulence of five wild-type influenza A viruses and 14 recombinant viruses, prepared from the cold adapted A/Ann Arbor/6/60 virus and various wild-type viruses, was studied by two methods. Firstly, the viruses were inoculated into hamsters, and the titres present in the lungs and turbinates at 1, 3 and 4 days post-infection were measured. Secondly, the effect of five wild-type and ten recombinant viruses on the ciliated epithelium of in vitro hamster tracheal organ cultures was examined. The results obtained were assessed with reference to the known virulence of the viruses for human volunteers. The results showed that virus strains virulent for man grew to higher titres in hamster lungs and turbinates than attenuated strains; and that virulent strains destroyed the ciliary activity of hamster tracheal organ cultures more quickly and to a greater extent than attenuated strains. Comparison of the results with the known virulence of viruses tested for man suggests that the reduced ability of virus to grow in hamster lung tissue and the relatively little effect on ciliary activity may be used as markers of virus attenuation; however, the growth of virus in hamster turbinates overlaps for virulent and attenuated strains and therefore was not considered a useful marker of virulence.