JMB-HEADER RAS-JOURNALS EIMB Pleiades Publishing

RUS

             

ENG

YearIMPACT-FACTOR
2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 50(2016) N 5 p. 755-761; DOI 10.1134/S0026893316050174 Full Text

T.A. Timofeeva1*, G.K. Sadykova1, I.A. Rudneva1, E.Y. Boravleva2, A.S. Gambaryan2, N.F. Lomakina2, L.V. Mochalova3, N.V. Bovin4, E.V. Usachev1, A.G. Prilipov1

Changes in the phenotypic properties of highly pathogenic influenza A virus of H5N1 subtype induced by N186I and N186T point mutations in hemagglutinin

1Gamaleya Federal Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098 Russia
2Chumakov Institute of Poliomyelitis and Viral Encephalitis, Russian Academy of Sciences, Moscow, 142782 Russia
3Belozersky Institute of Physicochemical Biology, Moscow State University, Moscow, 119991 Russia
4Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997 Russia

*timofeeva.tatyana@inbox.ru
Received - 2015-12-11; Accepted - 2016-01-06

The change in the phenotypic properties resulting from amino acid substitutions in the hemagglutinin (HA) molecule is an important link in the evolutionary process of influenza viruses. It is believed to be one of the mechanisms of the emergence of highly pathogenic strains of influenza A viruses, including subtype H5N1. Using the site-directed mutagenesis, we introduced mutations in the HA gene of the H5N1 subtype of influenza A virus. The obtained virus variants were analyzed and compared using the following parameters: optimal pH of conformational transition (according to the results of the hemolysis test), specificity of receptor binding (using a set of synthetic analogues of cell surface sialooligosaccharides), thermoresistance (heat-dependent reduction of hemagglutinin activity), virulence in mice, and the kinetics of replication in chicken embryos, and reproductive activity at different temperatures (RCT-based). N186I and N186T mutations in the HA protein increased the virulence of the original virus in mice. These mutations accelerated virus replication in the early stages of infection in chicken embryos and increased the level of replication at late stages. In addition, compared to the original virus, the mutant variants replicated more efficiently at lower temperatures. The obtained data clearly prove the effect of amino acid substitutions at the 186 position of HA on phenotypic properties of the H5N1 subtype of influenza A.

influenza A virus, hemagglutinin H5, amino acid substitutions, site-specific mutagenesis, phenotypic properties



JMB-FOOTER RAS-JOURNALS