scholarly journals Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses

2016 ◽  
Vol 12 (4) ◽  
pp. e1005526 ◽  
Author(s):  
William T. Harvey ◽  
Donald J. Benton ◽  
Victoria Gregory ◽  
James P. J. Hall ◽  
Rodney S. Daniels ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
High Impact ◽  
Antigenic Drift ◽  
Amino Acid Substitutions ◽  
Influenza A H1n1

scholarly journals MOLECULAR AND GENETIC CHARACTERISTICS OF SURFACE AND NONSTRUCTURE PROTEINS OF PANDEMIC INFLUENZA VIRUSES A(H1N1)PDM09 IN 2015-2016 EPIDEMIC SEASON

2016 ◽  
Vol 72 (2) ◽  
pp. 44-48
Author(s):  
O. Smutko ◽  
L. Radchenko ◽  
A. Mironenko
Keyword(s):  
Amino Acid ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Phylogenetic Trees ◽  
Influenza Viruses ◽  
Amino Acid Substitutions ◽  
Ns1 Protein ◽  
Genetic Characteristics ◽  
Epidemic Season ◽  
Influenza A H1n1

The aim of the present study was identifying of molecular and genetic changes in hemaglutinin (HA), neuraminidase (NA) and non-structure protein (NS1) genes of pandemic influenza A(H1N1)pdm09 strains, that circulated in Ukraine during 2015-2016 epidemic season. Samples (nasopharyngeal swabs from patients) were analyzed using real-time polymerase chain reaction (RTPCR). Phylogenetic trees were constructed using MEGA 7 software. 3D structures were constructed in Chimera 1.11.2rc software. Viruses were collected in 2015-2016 season fell into genetic group 6B and in two emerging subgroups, 6B.1 and 6B.2 by gene of HA and NA. Subgroups 6B.1 and 6B.2 are defined by the following amino acid substitutions. In the NS1 protein were identified new amino acid substitutions D2E, N48S, and E125D in 2015-2016 epidemic season. Specific changes were observed in HA protein antigenic sites, but viruses saved similarity to vaccine strain. NS1 protein acquired substitution associated with increased virulence of the influenza virus.

scholarly journals Amino Acid Substitutions Analysis of the Putative Epitopes of Neuraminidase Protein from Influenza A H1N1 Virus

2021 ◽  
Vol 22 (1) ◽  
pp. 1-16
Author(s):  
Ludmila Alves Dias Souto ◽  
Alessandra Rejane Ericsson de Oliveira Xavier ◽  
Mauro Aparecido de Sousa Xavier
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
H1n1 Virus ◽  
Epitope Prediction ◽  
Viral Population ◽  
Amino Acid Substitutions ◽  
Specific Amino Acid ◽  
Influenza A H1n1 ◽  
Virus Sequence ◽  
Clustal Omega

Objective: This study verified whether the neuraminidase protein of Influenza A H1N1 virus sequence has modified from 2009–2017 and its impact on the 2018 Brazilian vaccine. Method: The reference neuraminidase protein sequence from H1N1 Puerto Rico/1934 strain was subjected to three different methods of epitope prediction and the top five from each method were aligned using Clustal omega, resulting in eight putative epitopes. These epitopes were aligned to 7,438 neuraminidase sequences spanning from 2009–2017 and analyzed for specific amino acid substitutions and counted. The resultant neuraminidase protein was aligned against the 2015 and 2018 neuraminidase proteins, from Influenza A H1N1 virus subtypes, used for vaccine production. Result: Twenty-one main substitutions were detected, of which 16/21 (76.2%) substitutions points remained stable and 1/21 (4.8%) returned to the original amino acid residue in the viral population from 2009–2017. Additionally, 19% (4/21) substitutions occurred in Brazil and worldwide in this period, indicating that changes in the neuraminidase viral population profile is time-dependent rather than geographical. Conclusion: The neuraminidase protein containing these amino acid substitutions is more closely related to the neuraminidase protein from influenza A/Michigan/45/2015 than A/California/7/2009, supporting the replacement of this virus subtype in the Brazilian vaccine in 2018.

Influenza A (H1N1) vaccine efficacy in animal models is influenced by two amino acid substitutions in the hemagglutinin molecule

Virology ◽  
1989 ◽  
Vol 171 (1) ◽  
pp. 214-221 ◽  
Author(s):  
John M. Wood ◽  
John S. Oxford ◽  
Una Dunleavy ◽  
Robert W. Newman ◽  
Diane Major ◽  
...  
Keyword(s):  
Amino Acid ◽  
Animal Models ◽  
Vaccine Efficacy ◽  
Influenza A ◽  
Amino Acid Substitutions ◽  
H1n1 Vaccine ◽  
Influenza A H1n1

scholarly journals Amino acid substitutions in hemagglutinin of the 2009 pandemic influenza A(H1N1) viruses that might affect the viral antigenicity

2014 ◽  
Vol 7 (1) ◽  
pp. 951 ◽  
Author(s):  
Nathamon Kosoltanapiwat ◽  
Usa Boonyuen ◽  
Phisanu Pooruk ◽  
Sopon Iamsirithaworn ◽  
Anek Mungaomklang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Amino Acid Substitutions ◽  
Influenza A H1n1

scholarly journals The Molecular Determinants of Antigenic Drift in a Novel Avian Influenza A (H9N2) Variant Virus

2021 ◽  
Author(s):  
Yiqing Zheng ◽  
Yanna Guo ◽  
Yingfei Li ◽  
Bing Liang ◽  
Xiaoyuan Sun ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Avian Influenza ◽  
Vaccine Strain ◽  
Influenza A ◽  
Immune Escape ◽  
Antigenic Drift ◽  
Amino Acid Substitutions ◽  
Variant Virus ◽  
Molecular Determinants

Abstract Background: In early 2020, a novel H9N2 AIV immune escape variant emerged in South China and rapidly spread throughout mainland China. The effectiveness of the current H9N2 vaccine is being challenged by emerging immune escape strains. Assessing key amino acid substitutions that contribute to antigenic drift and immune escape in the HA gene of circulating strains is critical for understanding virus evolution and in selecting more effective vaccine components. Methods: In this study, a representative immune escape strain, A/chicken/Fujian/11/2020 (FJ/20), differed from current H9N2 vaccine strain, A/chicken/Anhui/LH99/2017 (AH/17) by 18 amino acids in the head domain. To investigate the molecular determinants of antigenic drift of FJ/20, a panel of mutants were generated by reverse genetics including specific amino acids changes in the HA genes of FJ/20 and AH/17. The antigenic effect of the substitutions was evaluated by hemagglutination inhibition (HI) assay and antigenic cartography. Results: Fujian-like H9N2 viruses had changed antigenicity significantly, having mutated into an antigenically distinct sub-clade. Relative to the titers of the vaccine virus AH/17, the escape strain FJ/20 saw a 16-fold reduction in HI titer against antiserum elicited by AH/17. Our results showed that seven residue substitutions (D127S, G135D, N145T, R146Q, D179T, R182T and T183N) near the HA receptor binding sites were critical for converting the antigenicity of both AH/17 and FJ/20. Especially, the combined mutations 127D, 135G, 145N, and 146R could be a major factor of antigenic drift in the current immune escape variant FJ/20. The avian influenza A (H9N2) variant virus need further ongoing epidemiological surveillance.Conclusions: In this study, we evaluated the relative contributions of different combinations of amino acid substitutions in the HA globular head domain of the immune escape strain FJ/20 and the vaccine strain AH/17. Our study provides more insights into the molecular mechanism of the antigenic drift of the H9N2 AIV immune escape strain. This work identified important markers for understanding H9N2 AIV evolution as well as for improving vaccine development and control strategies in poultry.

scholarly journals Analysis of influenza A virus reinfection in children in Japan during 1983–91

1995 ◽  
Vol 115 (3) ◽  
pp. 591-601 ◽  
Author(s):  
S. Nakajima ◽  
F. Nishikawa ◽  
K. Nakamura ◽  
K. Nakajima
Keyword(s):  
Amino Acid ◽  
Influenza A Virus ◽  
Influenza A ◽  
Haemagglutination Inhibition ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
H3n2 Virus ◽  
Influenza B ◽  
Influenza A H1n1 ◽  
Influenza H3n2

SummaryThe epidemiology of influenza A in Japan was studied during 1979–91 and viruses isolated from reinfections during 1983–91 were analysed, Of 2963 influenza viruses isolated during this period, 922 and 1006 were influenza A(H1N1) and A(H3N2) viruses respectively; the others were influenza B viruses. Influenza A(H1N1) and A(H3N2) caused 5 and 6 epidemics respectively, most accompanied by antigenic drift. Seventeen reinfections with H1N1 and 17 with H3N2 were detected during our study. The primary and reinfection strains isolated from 7 H1N1 and 10 H3N2 cases were studied by haemagglutination-inhibition, and amino acid and nucleotide sequences of the HA1 region of the haemagglutinin. Most of the primary and reinfection strains were antigenically and genetically similar to the epidemic viruses circulating at that time. However, in 4 out of 10 cases of reinfection with influenza H3N2 virus, reinfection strains were genetically different from the epidemic viruses.

Pleiotropic effects of hemagglutinin amino acid substitutions of influenza A(H1N1)pdm09 virus escape mutants

2018 ◽  
Vol 251 ◽  
pp. 91-97 ◽  
Author(s):  
Irina A. Rudneva ◽  
Tatiana A. Timofeeva ◽  
Evgenia A. Mukasheva ◽  
Anna V. Ignatieva ◽  
Aleksandr A. Shilov ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Pleiotropic Effects ◽  
Amino Acid Substitutions ◽  
Virus Escape ◽  
Pdm09 Virus ◽  
Influenza A H1n1 ◽  
Escape Mutants

scholarly journals Plasticity of Amino Acid Residue 145 Near the Receptor Binding Site of H3 Swine Influenza A Viruses and Its Impact on Receptor Binding and Antibody Recognition

2018 ◽  
Vol 93 (2) ◽  
Author(s):  
Jefferson J. S. Santos ◽  
Eugenio J. Abente ◽  
Adebimpe O. Obadan ◽  
Andrew J. Thompson ◽  
Lucas Ferreri ◽  
...  
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Influenza A ◽  
Antigenic Drift ◽  
Amino Acid Substitutions ◽  
Receptor Binding Site ◽  
Antibody Recognition ◽  
Antigenic Characterization ◽  
Antigenic Evolution

ABSTRACT The hemagglutinin (HA), a glycoprotein on the surface of influenza A virus (IAV), initiates the virus life cycle by binding to terminal sialic acid (SA) residues on host cells. The HA gradually accumulates amino acid substitutions that allow IAV to escape immunity through a mechanism known as antigenic drift. We recently confirmed that a small set of amino acid residues are largely responsible for driving antigenic drift in swine-origin H3 IAV. All identified residues are located adjacent to the HA receptor binding site (RBS), suggesting that substitutions associated with antigenic drift may also influence receptor binding. Among those substitutions, residue 145 was shown to be a major determinant of antigenic evolution. To determine whether there are functional constraints to substitutions near the RBS and their impact on receptor binding and antigenic properties, we carried out site-directed mutagenesis experiments at the single-amino-acid level. We generated a panel of viruses carrying substitutions at residue 145 representing all 20 amino acids. Despite limited amino acid usage in nature, most substitutions at residue 145 were well tolerated without having a major impact on virus replication in vitro. All substitution mutants retained receptor binding specificity, but the substitutions frequently led to decreased receptor binding. Glycan microarray analysis showed that substitutions at residue 145 modulate binding to a broad range of glycans. Furthermore, antigenic characterization identified specific substitutions at residue 145 that altered antibody recognition. This work provides a better understanding of the functional effects of amino acid substitutions near the RBS and the interplay between receptor binding and antigenic drift. IMPORTANCE The complex and continuous antigenic evolution of IAVs remains a major hurdle for vaccine selection and effective vaccination. On the hemagglutinin (HA) of the H3N2 IAVs, the amino acid substitution N 145 K causes significant antigenic changes. We show that amino acid 145 displays remarkable amino acid plasticity in vitro, tolerating multiple amino acid substitutions, many of which have not yet been observed in nature. Mutant viruses carrying substitutions at residue 145 showed no major impairment in virus replication in the presence of lower receptor binding avidity. However, their antigenic characterization confirmed the impact of the 145 K substitution in antibody immunodominance. We provide a better understanding of the functional effects of amino acid substitutions implicated in antigenic drift and its consequences for receptor binding and antigenicity. The mutation analyses presented in this report represent a significant data set to aid and test the ability of computational approaches to predict binding of glycans and in antigenic cartography analyses.

scholarly journals Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

2015 ◽  
Vol 89 (7) ◽  
pp. 3763-3775 ◽  
Author(s):  
Björn F. Koel ◽  
Ramona Mögling ◽  
Salin Chutinimitkul ◽  
Pieter L. Fraaij ◽  
David F. Burke ◽  
...  
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Amino Acid Substitutions ◽  
Receptor Binding Site ◽  
Population Immunity ◽  
Influenza A H1n1 ◽  
Hemagglutinin Protein ◽  
2009 Influenza Pandemic

ABSTRACTThe majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiencyin vitrocompared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity.IMPORTANCEInfluenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as a result of increasing population immunity. We show that single amino acid substitutions near the receptor binding site were sufficient to escape from antibodies specific for A(H1N1)pdm09 viruses but not from antibodies elicited in response to infections with seasonal A(H1N1) and A(H1N1)pdm09 viruses. This study identified substitutions in A(H1N1)pdm09 viruses that support escape from population immunity but also suggested that the number of potential escape variants is limited by previous exposure to seasonal A(H1N1) viruses.

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