Studies on the genetic determinants of influenza virus pathogenicity for mice with the use of reassortants between mouse-adapted and non-adapted variants of the same virus strain

The original influenza virus strain A/USSR/90/77 (H 1 N 1) and its mouse-adapted variant, differing in their reactivity with anti-hemagglutinin monoclonal antibodies HC 22 and HC 124, were crossed in MDCK cells and in chicken embryos, and 21 clones were isolated by non-selective random cloning. In all the clones the virulence for mice was found to be linked to the antigenic specificity of hemagglutinin (HA). An independent marker, formation of filamentous forms, was reassorted with an expected frequency. In the crosses between UV-irradiated mouse-adapted variant and live non-adapted strain, with selection of clones by a mixture of monoclonal antibodies discriminating between HA of the two variants, virulence also was linked to HA gene. On the contrary, in the experiments with A/Aichi/2/68 (H 3 N 2) strain and its mouse-adapted highly virulent variant these two characteristics--virulence and HA antigenic specificity--could be dissociated. A pathogenic clone having HA of the non-adapted strain was readily obtained; its virulence, however, was weaker than that of the mouse-adapted parent. In the inter-subtypic crosses between A/USSR/90/77 and A/Aichi/2/68 the transfer of the HA gene of the mouse-adapted A/Aichi/2/68 did not confer virulence to the reassortant. The results are discussed in terms of the genetic basis of virulence acquired in the course of influenza virus adaptation to a new host.