Cold-adapted Reassortants of Influenza A Virus: Pathogenicity of A/Ann Arbor/6/60 X A/Alaska/6/77 Reassortant Viruses in Vivo and in Vitro

Cold-adapted reassortants of A/Ann Arbor/6/60 X A/Alaska/6/77 viruses made in MDCK cells have recently been assessed genotypically and for temperature-sensitive and cold-adapted phenotypes. These reassortants were used to infect ferrets and hamsters and to inoculate organ cultures of hamster tracheal rings, in order to assess their degree of virulence. Virulence in the three model systems corresponded quite well, and a correlation between loss of virulence and particular A/AA/6/60 genes present in the reassortants was noted. Two different reassortants containing either RNA 2 or RNA 5 (NA gene) alone from A/AA/6/60 showed little attenuation from the wild-type parent. A reassortant containing both RNA 2 and the NA gene from A/AA/6/60 and all remaining wild-type genes showed some small decrease in virulence compared to the wild-type virus. However a reassortant containing these two A/AA/6/60 genes and RNA 3 as an additional gene from this parent, had a level of attenuation comparable to that of the cold-adapted virus.