MUTATIONS IN HEMAGGLUTININ ACCOMPANYING I NFLUENZA-VIRUS ADAPTATION TO MICE AND THEIR ROLE IN ACQUIRING VIRULENT PROPERTIES AND RESISTANCE TO SERUM INHIBITORS

Passages of influenza A/USSR/90/77 virus in mouse lungs produced a vir ulent virus (18th passage) carrying two mutations in hemagglutinin (HA ) Asn127 --> Asp and Tre89 --> Ala. Cloning of this virus revealed two avirulent clones in the population. The analysis of one virulent (clo ne 7p) and one avirulent (clone 31 np) clones showed them to have both abovementioned substitutions in HA. Clone 7p replicated in mouse lung s much more effectively than clone 31np, the difference in titres bein g 2 log10 EID50. In another experiment, the adapted virus (15th passag e) did not differ in its antigenic, virulent, and reproductive propert ies from clone 7p but had only one substitution in HA Asn127 --> Asp. Consequently, adaptation to mice required at least one mutation in HA resulting in the loss of glycosylation site. However, acquirement of v irulence requires additional factors affecting the level of virus repr oduction. Examinations of a number of normal animal sera and erythrocy tes showed the mutations in HA accompanying virus adaptation to mice l ed to the development of resistance to serum inhibitors and changes in the receptor-binding specificity. These properties may be also associ ated with the loss of glycosylation site in the receptor-binding regio n of hemagglutinin molecule.