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Mol Biol (Mosk). 2016 Sep-Oct;50(5):855-862.

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

[Article in Russian]

Author information

1
Gamaleya Federal Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098 Russia.
2
timofeeva.tatyana@inbox.ru.
3
Chumakov Institute of Poliomyelitis and Viral Encephalitis, Russian Academy of Sciences, Moscow, 142782 Russia.
4
Belozersky Institute of Physicochemical Biology, Moscow State University, Moscow, 119991 Russia.
5
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997 Russia.

Abstract

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.

KEYWORDS:

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

PMID:
27830688
DOI:
10.7868/S0026898416050177
[Indexed for MEDLINE]
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