[Changes in its hemagglutinin during the adaptation of the influenza virus to mice and their role in the acquisition of virulent properties and resistance to serum inhibitors].
Passages of influenza A/USSR/90/77 virus in mouse lungs produced a virulent 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 (clone 7p) and one avirulent (clone 31 np) clones showed them to have both above-mentioned substitutions in HA. Clone 7p replicated in mouse lungs much more effectively than clone 31np, the difference in titres being 2 log10 EID50. In another experiment, the adapted virus (15th passage) did not differ in its antigenic, virulent, and reproductive properties 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 virulence requires additional factors affecting the level of virus reproduction. Examinations of a number of normal animal sera and erythrocytes showed the mutations in HA accompanying virus adaptation to mice led to the development of resistance to serum inhibitors and changes in the receptor-binding specificity. These properties may be also associated with the loss of glycosylation site in the receptor-binding region of hemagglutinin molecule.
Shilov
A A
AA
Sinitsyn
B V
BV
D000222:Adaptation, Physiological / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000037:antagonists & inhibitors*; D001483:Base Sequence; D002642:Chick Embryo; D005814:Genes, Viral / Q000235:genetics; D014644:Genetic Variation; D006389:Hemagglutinins, Viral / Q000235:genetics* / Q000276:immunology; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D008168:Lung / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D012692:Serial Passage; D014774:Virulence / Q000235:genetics / Q000276:immunology; D014776:Virus Cultivation
D000998:Antiviral Agents; D006389:Hemagglutinins, Viral
Izmeneniia v gemaggliutinine pri adaptatsii virusa grippa k mysham i ikh rol' v priobretenii virulentnykh svoĭstv i ustoĭchivosti k syvorotochnym ingibitoram.