Effect of amino acid substitutions in the small subunit of the avian H5N2 influenza virus hemagglutinin on selection of the mutants, resistant to neutralizing monoclonal antibodies

• DOI: 10.1134/s002689331502003x
• Publication Date: 2015-04-14T20:45:58Z
• Authors: A. V. Ignatieva; T. A. Timofeeva; I. A. Rudneva; A. A. Shilov; O. V. Masalova; R. R. Klimova; A. A. Kushch; N. A. Ilyushina; N. V. Kaverin
• Keywords: 0301 basic medicine; Mutation, Missense; Hemagglutinin Glycoproteins, Influenza Virus; Chick Embryo; Antibodies, Viral; Antibodies, Neutralizing; 3. Good health; Antibodies, Monoclonal, Murine-Derived; 03 medical and health sciences; Amino Acid Substitution; Influenza in Birds; Animals; Influenza A Virus, H5N2 Subtype; Chickens

Changes associated with the resistance to physical and chemical factors in the hemagglutinin (HA) of influenza A viruses may play an important role in the selection of different influenza variants during circulation in nature. Here, we studied the escape mutants of influenza virus A/mallard/Pennsylvania/10218/84 (H5N2) that were selected by the monoclonal antibody. The escape mutant m4F11(4) carried a single amino acid substitution in large subunit (HA1) of the HA, S145P1, and two ones, m4G10(10) and m4G10(6), had additional amino acid changes in the small subunit (HA2), namely: L124F2 and L124F2 + N79D2, respectively. As it has been found the substitutions appeared in the HA2 of m4G(10) and m4G(6) viruses compensated negative effect of the S145P1 mutation and provided a significant increase in the viral replication ability at the early stage of infection in embryonated chicken eggs as well as in HA thermostability in comparison with m4F11(4) mutant. Phenotypic properties that provide advantages in the process of virus replication can play a role of the positive selection factor in viral population.