Evolution of pandemic influenza virus A(H1N1)pdm09 in 2009-2016: dynamics of receptor specificity of the first hemagglutinin subunit (HA1)

INTRODUCTION: The new reassortant of the swine flu virus A(H1N1)pdm09, which emerged in 2009, overcame the species barrier and caused the 2009-2010 pandemic. One of the key points required for the influenza virus to overcome the species barrier and adapt it to humans is its specific binding to the receptors on the epithelium of the human respiratory tract. PURPOSE: Studying the dynamics of changes in receptor specificity (RS) of the HA1 subunit of the hemagglutinin of the influenza A(H1N1)pdm09 virus strains isolated during the period 2009-2016 on the territory of the Russian Federation, and an analysis of the possible impact of these changes on the incidence rates of the population of the Russian Federation of pandemic influenza in certain epidemic seasons. MATERIAL AND METHODS: Standard methods of collecting clinical materials, isolation of influenza viruses, their typing and genome sequencing were used. For the study of RS of influenza A virus (H1N1)pdm09, the method of solid phase sialosidenzyme analysis was used. RESULTS: It is shown that the change in the parameter W3/6 , which characterizes the degree of a2-3 receptor specificity (a2-3-RS) of the influenza virus A(H1N1) pdm09 over a2-6-RS, coincides with the change in the incidence rates of the Russian Federation's pandemic flu in separate epidemic seasons. There is a tendency to increase the affinity of the virus A(H1N1)pdm09 to α2-3 analogs of the sialyl-glycan receptors of the human respiratory tract epithelium - α2-3-sialoglycopolymers (α2-3-SGP), and falls to α2-6-SGP, with the virus showing the greatest affinity for sulfated sialoglycopolymers. DISCUSSION: Screening for RS strains of influenza A (H1N1)pdm09 virus isolated on the territory of the Russian Federation in 2009-2016 revealed a decrease in the affinity of viruses for a2-6-sialosides, especially for 6'SL-SGP, which is probably due to the presence of amino acid substitutions in the 222 and 223 positions of RBS HA1 viruses. Previous studies have shown that the presence of such substitutions correlates with an increase in the virulence of the influenza A virus (H1N1)pdm09 [16, 23]. Probably, the pandemic virus has evolved towards the selection of more virulent pneumotropic variants. CONCLUSION: Monitoring of the receptor specificity of a pandemic influenza virus makes it possible to identify strains with altered RS to the epithelium of the human respiratory tract and an increased ability to transfer from person to person. Change in the period 2009-2016 the W3/6 parameter characterizing the degree of α2-3-RS excess of the influenza A(H1N1)pdm09 virus over α2-6-RS, coincides with the change in the incidence rates of the pandemic influenza population of the Russian Federation in certain epidemic seasons.

Lvov D.K.1 , Bogdanova V.S.1 , Kirillov I.M.1 , Shchelkanov M.Y.2 , Burtseva E.I.1 , Bovin N.V.3 , Fedyakina I.T.1 , Prilipov A.G.1 , Alhovsky S.V.1 , Samokhvalov E.I. 1 , Proshina E.S.1 , Kirillova E.S.1 , Syroeshkin A.V. 4
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  • 1 Ivanovsky Institute of Virology «National Research Centre for Epidemiology and Microbiology named honorary academician N.F. Gamaleya», Moscow, 123098, Russian Federation
  • 2 Far Eastern Federal University, Vladivostok, 690950, Russian Federation
  • 3 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russian Federation
  • 4 Peoples Frendship University of Russia (RUDN), Moscow, 117198, Russian Federation
epidemic season; hemagglutinin (HA); influenza; influenza virus A(H1N1)pdm09; receptor specificity; sialoglycopolymer (SGP); sialyl-glycan receptor
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