CHANGE OF PHENOTYPIC PROPERTIES OF ESCAPE MUTANTS AND READAPTANTS OF INFLUENZA VIRUS A (H1N1) PDM09 UNDER THE INFLUENCE OF SELECTED MUTATIONS IN THE MOLECULE OF HEMAGGLUTININ

Abstract

Introduction. After the emergence and spread of pandemic H1N1 viruses in 2009, antigenic epitopes recognized by neutralizing antibodies against the hemagglutinin of influenza A/Moscow/01/09(H1N1)pdm09 viruses were studied. Targets and goals. The purpose of the study was to obtain readapted variants of the virus from a low-virulent escape-mutant that has an increased affinity of the avian and the human types cellular receptors compared to the wild type and the comparative study of their antigenic and receptor specificity. Material and methods. Viruses were accumulated in 10-day-old chicken embryos. The MAB panel against HA of influenza virus strain A/IIV-Moscow/01/09(H1N1)sw1 was used in the form of ascites fluids from mice. Immunization of mice, HI testing, elution of viruses from chicken erythrocytes, PCR and sequencing of readapted variants were performed by standard methods. Results. The amino acid substitution A198E acquired in the process of readaptation leads to changes in the antigenic specificity. A correlation was found between a decrease in virulence of a low-virulent escape mutant associated with the substitution D190N in the hemagglutinin molecule and an increase in the hemagglutinating titer to inhibitors in normal mouse serum. Viruses with low affinity of cellular receptor analogs and carrying amino acid substitutions have an increased ability to elute from chicken erythrocytes. Discussion. The results discuss the effect of mutations in the HA molecule of the influenza A(H1N1)pdm09 virus to the change in antigen specificity; virulence for mice, adsorption-elution at cellular receptors. Conclusion. A comparative study of the antigenic specificity and receptor-binding activity of the escape mutants was conducted for the hemagglutinin of the influenza virus A/Moscow/01/2009 (H1N1)swl, and the readapted variants obtained for one of the escape mutants with reduced virulence for mouse. Monitoring the pleiotropic effect of mutations in the hemagglutinin H1 molecule is necessary to predict variants of the virus with pandemic potential.