| Autor: |
Lyashko AV; The Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia., Timofeeva TA; The Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia., Rudneva IA; The Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia., Lomakina NF; The Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia., Treshchalina AA; Federal Scientific Center for the Research and Development of Immune-and-Biological Products, 108819 Moscow, Russia., Gambaryan AS; Federal Scientific Center for the Research and Development of Immune-and-Biological Products, 108819 Moscow, Russia., Sorokin EV; The Smorodintsev Research Institute of Influenza, the Ministry of Health of the Russian Federation, 197376 St. Petersburg, Russia., Tsareva TR; The Smorodintsev Research Institute of Influenza, the Ministry of Health of the Russian Federation, 197376 St. Petersburg, Russia., Adams SE; Institute of Microbiology, Lausanne University Hospital, 1011 Lausanne, Switzerland., Prilipov AG; The Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia., Sadykova GK; The Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia., Timofeev BI; The Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia., Logunov DY; The Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia., Gintsburg AL; The Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia. |
| Abstrakt: |
The North American low pathogenic H7N2 avian influenza A viruses, which lack the 220-loop in the hemagglutinin (HA), possess dual receptor specificity for avian- and human-like receptors. The purpose of this work was to determine which amino acid substitutions in HA affect viral antigenic and phenotypic properties that may be important for virus evolution. By obtaining escape mutants under the immune pressure of treatment with monoclonal antibodies, antigenically important amino acids were determined to be at positions 125, 135, 157, 160, 198, 200, and 275 (H3 numbering). These positions, except 125 and 275, surround the receptor binding site. The substitutions A135S and A135T led to the appearance of an N-glycosylation site at 133N, which reduced affinity for the avian-like receptor analog and weakened binding with tested monoclonal antibodies. Additionally, the A135S substitution is associated with the adaptation of avian viruses to mammals (cat, human, or mouse). The mutation A160V decreased virulence in mice and increased affinity for the human-type receptor analog. Conversely, substitution G198E, in combination with 157N or 160E, displayed reduced affinity for the human-type receptor analog. |
