Studies on the genetic basis of human influenza A virus adaptation to mice: degrees of virulence of reassortants with defined genetic content.

A highly virulent mouse-adapted variant of influenza virus A/Aichi/2/68 (H3N2) was crossed either with the original A/USSR/90/77 (H1N1) influenza virus strain or with its mouse-adapted, moderately mouse virulent variant. The reassortants were characterized with respect to their genetic content and pneumovirulence for mice. The reassortants fell into three categories: avirulent, highly virulent (resembling in this respect the parent A/Aichi/2/68 virus) and moderately virulent (resembling the mouse-adapted A/USSR/90/77 parent virus). The analysis of the parental origin of the genes of 6 reassortants allowed to suggest that changes in the HA gene and in a polymerase gene (most likely, PB1) were necessary for the acquisition of virulence by the A/USSR/90/77 virus in the course of adaptation to mice, whereas the changes in two other polymerase genes as well as in the genes NA and NS were not involved. The low degree of pathogenicity characteristic of the mouse-adapted A/USSR/90/77 virus was determined by gene(s) other than HA.