Variability of nonpathogenic influenza virus H5N3 under immune pressure

Abstract

Mutations arising in influenza viruses that have undergone immune pressure may promote a successful spread of mutants in nature. In order to evaluate the variability of nonpathogenic influenza virus A/duck/Moscow/4182-C/2010(H5N3) and to determine the common epitopes between it and highly pathogenic H5N1 avian influenza viruses (HPAIV), a set of escape mutants was selected due to action of MABs specific against A/chicken/Pennsylvania/8125/83(H5N2), A/Vietnam/1203/04(H5N1) and A/duck/ Novosibirsk/56/05(H5N1) viruses. The complete genomes of escape mutants were sequenced and amino acid point mutations were determined in HA, NA, PA, PB1, PB2, M1, M2, and NP proteins. Comprehensive analysis of the acquired mutations was performed using the Influenza Research Database (https://www. fludb.org) and revealed that all mutations were located inside short linear epitopes, in positions characterized by polymorphisms. Most of the mutations found were characterized as substitutions by predominant or alternative amino acids existing in nature. Antigenic changes depended only on substitutions at positions 126, 129, 131, 145 and 156 of HA (H3 numbering). The positions 126, 145 and 156 were common for HA/H5 of different phylogenetic lineages of H5N1 HPAIV (arisen from A/goose/Guangdong/1/96) and low pathogenic American and Eurasian viruses. Additionally, mutation S145P increased the temperature of HA heat inactivation, compared to wild-type, as was proved by reverse genetics. Moreover, nonpathogenic A/ duck/Moscow/4182-C/2010(H5N3) and H5N1 HPAI viruses have the same structure of short linear epitopes

Antigenic Architecture of the H7N2 Influenza Virus Hemagglutinin Belonging to the North American Lineage

“…The mouse-adapted virus A/chicken/NJ/294598-12MA/2004 (H7N2) (MA/NJ) was obtained by serial passages of the original chicken wild-type A/chicken/NJ/294598-12/2004 (H7N2) (ch/NJ) virus in the lungs of mice [ 27 ]. The MA/NJ virus was used as the initial virus to produce escape mutants that have avoided immune pressure and survived in the presence of MABs.…”

“…In addition to the mutations acquired in HA during the initial adaptation of the chicken influenza virus ch/NJ to mice, the MA/NJ virus acquired one in PB2, E627K [ 27 ]. All of the escape mutants characterized here have retained this mutation in PB2.…”

“…Some amino acid changes in antigenically significant positions of HA have pleiotropic properties and can affect other phenotypic features such as receptor binding, HA thermal stability, the optimal fusion pH (HA activation), or the virulence. All of these alterations can contribute to the expansion of the viral host range, survival of the virus under new conditions, and may promote its evolution, as was shown for H5 viruses [ 24 , 25 , 26 ].…”

Competitive fitness and homologous recombination of SARS‐CoV‐2 variants of concern

“…These findings illustrate that the effects of the viral fitness for the competition among SARS‐CoV‐2 variants is not always the same. Immune pressure represents another driving factor that promotes the generation of novel variants of some pathogenic viruses 15–18 . Recently, Ravindra K Gupta confirmed that convalescent plasma treatment for immune‐suppressed individuals led to the emergence of SARS‐CoV‐2 variants with reduced susceptibility to neutralizing antibodies 19 .…”

“…Immune pressure represents another driving factor that promotes the generation of novel variants of some pathogenic viruses. [15][16][17][18] Recently, Ravindra K Gupta confirmed that convalescent plasma treatment for immune-suppressed individuals led to the emergence of SARS-CoV-2 variants with reduced susceptibility to neutralizing antibodies. 19 However, whether immune selection pressure contributes to the emergence and displacement of SARS-CoV-2 epidemic variants lacks direct evidence.…”