Identification of Hemagglutinin Residues Responsible for H3N2 Antigenic Drift during the 2014–2015 Influenza Season

Chambers, Benjamin S.; Parkhouse, Kaela; Ross, Ted M.; Alby, Kevin; Hensley, Scott E.

doi:10.1016/j.celrep.2015.06.005

Cited by 178 publications

(196 citation statements)

References 17 publications

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“…Our findings provide additional evidence that residues near the HA RBS, especially those in antigenic site B, play significant role in the antigenic evolution of H3N2 viruses (23,24). Seasonal H3N2 viruses experience antigenic drift, which necessitates frequent updates of H3N2 candidate viruses for seasonal influenza vaccines (24,29). Antigenic drift of H3N2 viruses is often due to single-or double-amino-acid mutations at several positions in the HA, e.g., 145, 155, 156, 158, 189, and 193 (24).…”

Section: Discussionmentioning

confidence: 90%

“…antigenic phenotype of A(H3N2)v viruses. Residues 155, 156, 158, 189, and 193 in antigenic site B of MN/10 HA were examined because these residues are commonly associated with antigenic drift of human seasonal and swine influenza viruses (23,24,28,29). Reassortant MN/10 viruses bearing each of the 5 single mutations from MN/10 to BJ/92, Y155H, N156K, N158E, K189R, or K193S, were inhibited by MN/10 antiserum at slightly lower HI titers (160, 226, or 320) than wt MN/10.…”

Section: Resultsmentioning

confidence: 99%

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Amino Acids in Hemagglutinin Antigenic Site B Determine Antigenic and Receptor Binding Differences between A(H3N2)v and Ancestral Seasonal H3N2 Influenza Viruses

Wang

Ilyushina

Lugovtsev

et al. 2017

J Virol

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Influenza A H3N2 variant [A(H3N2)v] viruses, which have caused human infections in the UnitedStates in recent years, originated from human seasonal H3N2 viruses that were introduced into North American swine in the mid-1990s, but they are antigenically distinct from both the ancestral and current circulating H3N2 strains. A reference A(H3N2)v virus, A/Minnesota/11/2010 (MN/10), and a seasonal H3N2 strain, A/Beijing/32/1992 (BJ/92), were chosen to determine the molecular basis for the antigenic difference between A(H3N2)v and the ancestral viruses. Viruses containing wild-type and mutant MN/10 or BJ/92 hemagglutinins (HAs) were constructed and probed for reactivity with ferret antisera against MN/10 and BJ/92 in hemagglutination inhibition assays. Among the amino acids that differ between the MN/10 and BJ/92 HAs, those in antigenic site A had little impact on the antigenic phenotype. Within antigenic site B, mutations at residues 156, 158, 189, and 193 of MN/10 HA to those in BJ/92 switched the MN/10 antigenic phenotype to that of BJ/ 92. Mutations at residues 156, 157, 158, 189, and 193 of BJ/92 HA to amino acids present in MN/10 were necessary for BJ/92 to become antigenically similar to MN/ 10. The HA amino acid substitutions responsible for switching the antigenic phenotype also impacted HA binding to sialyl receptors that are usually present in the human respiratory tract. Our study demonstrates that antigenic site B residues play a critical role in determining both the unique antigenic phenotype and receptor specificity of A(H3N2)v viruses, a finding that may facilitate future surveillance and risk assessment of novel influenza viruses. IMPORTANCE Influenza A H3N2 variant [A(H3N2)v] viruses have caused hundreds of human infections in multiple states in the UnitedStates since 2009. Most cases have been children who had contact with swine in agricultural fairs. These viruses originated from human seasonal H3N2 viruses that were introduced into the U.S. swine population in the mid-1990s, but they are different from both these ancestral viruses and current circulating human seasonal H3N2 strains in terms of their antigenic characteristics as measured by hemagglutination inhibition (HI) assay. In this study, we identified amino acids in antigenic site B of the surface glycoprotein hemagglutinin (HA) that explain the antigenic difference between A(H3N2)v and the ancestral H3N2 strains. These amino acid mutations also alter binding to minor human-type glycans, suggesting that host adaptation may contribute to the selection of antigenically distinct H3N2 variants which pose a threat to public health.

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Section: Discussionmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Amino Acids in Hemagglutinin Antigenic Site B Determine Antigenic and Receptor Binding Differences between A(H3N2)v and Ancestral Seasonal H3N2 Influenza Viruses

Wang

Ilyushina

Lugovtsev

et al. 2017

J Virol

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“…Clades 3C.2a and 3C.3a were reported to harbor HA antigenic drift variants and each has a different substitution at amino acid residue position 159 (nucleotide triplet 475 to 477) that resides at the receptor-binding site of HA (21). With a few exceptions, clade 3C.2a viruses carry amino acid substitution F159Y (TTC¡TAC), while clade 3C.3a viruses contain F159S (TTC¡TCC) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Initial information gained from HI data indicated antigenic differences between the vaccine strain, A/Texas/50/2012, and circulating viruses from two H3 clades, 3C.2a and 3C.3a. Notably, viruses from these two clades often displayed a diminished ability to agglutinate red blood cells, thereby hindering the ability to test them in the HI assay (21). Therefore, monitoring the spread of these antigenically drifted viruses requires sequencing and phylogenetic analysis of the HA genes.…”

mentioning

confidence: 99%

A Pyrosequencing-Based Approach to High-Throughput Identification of Influenza A(H3N2) Virus Clades Harboring Antigenic Drift Variants

et al. 2017

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The rapid evolution of influenza A(H3N2) viruses necessitates close monitoring of their antigenic properties so the emergence and spread of antigenic drift variants can be rapidly identified. Changes in hemagglutinin (HA) acquired by contemporary A(H3N2) viruses hinder antigenic characterization by traditional methods, thus complicating vaccine strain selection. Sequence-based approaches have been used to infer virus antigenicity; however, they are time consuming and midthroughput. To facilitate virological surveillance and epidemiological studies, we developed and validated a pyrosequencing approach that enables identification of six HA clades of contemporary A(H3N2) viruses. The identification scheme of viruses of the H3 clades 3C.2, 3C.2a, 3C.2b, 3C.3, 3C.3a, and 3C.3b is based on the interrogation of five single nucleotide polymorphisms (SNPs) within three neighboring HA regions, namely 412 to 431, 465 to 481, and 559 to 571. Two bioinformatics tools, IdentiFire (Qiagen) and FireComb (developed in-house), were utilized to expedite pyrosequencing data analysis. The assay's analytical sensitivity was 10 focus forming units, and respiratory specimens with threshold cycle (C T ) values of Ͻ34 typically produced good quality pyrograms. When applied to 120 A(H3N2) virus isolates and 27 respiratory specimens, the assay displayed 100% agreement with clades determined by HA sequencing coupled with phylogenetics. The multi-SNP analysis described here was readily adopted by another laboratory with pyrosequencing capabilities. The implementation of this approach enhanced the findings from virological surveillance and epidemiological studies between 2013 and 2016, which examined more than 3,000 A(H3N2) viruses.KEYWORDS A(H3N2), genotyping, influenza, pyrosequencing S ince their introduction into the human population in 1968, influenza A(H3N2) viruses have been responsible for seasonal epidemics and associated with both a prolonged duration of the epidemic season and a greater disease severity (1-4). The hemagglutinin (HA) glycoprotein is the major surface antigen of influenza viruses; it is also responsible for the receptor binding and membrane fusion required for entrance into susceptible host cells (5). Decades ago, this glycoprotein was named "hemagglutinin" for its ability to bind and bridge erythrocytes. The other surface antigen, neuraminidase (NA), is a receptor-destroying enzyme (6). As with other seasonal influenza viruses, A(H3N2) viruses undergo genetic and antigenic changes, called antigenic drift,

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“…the wHo report shows that the dominant influenza virus in the 2014/15 influenza season in the northern hemisphere was a/H3n2/, with the exception of Slovenia (where a/H1n1/pdm09 prevailed) and Georgia and ukraine, where the dominant virus was a type b influenza strain [8][9][10][11].…”

Section: Methodsmentioning

confidence: 99%

A comparative analysis of influenza virus infections in the 2013/2014 and 2014/2015 epidemic seasons in the reporting system, for different age groups in Poland

Hallmann-Szelińska¹,

Rabczenko²,

Bednarska³

et al. 2016

fmpcr

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Background. Influenza remains the cause of many seasonal infections, leading even to death, in all age groups, for all patient health states, under all health policies, and in all latitudes. Influenza infection needs to be thought of not only in terms of the loss of health and the exacerbation of existing diseases, but also in terms of the quantifiable financial consequences borne by the state. Objectives. the aim of the study was to compare two influenza seasons: 2013/14 and 2014/15 through an analysis of the number of samples in different age groups, collected on a weekly basis for 52 weeks, and to interpret the results in terms of type and subtype. Material and methods. Virological and epidemiological data were obtained from the SEntinEl and non-SEntinEl programs. Virological tests were performed using Rt-PcR and multiplex Rt-PcR biological molecular methods. Results. the maximum number of confirmed cases of influenza coincides in time with the maximum number declared cases and suspected cases of influenza and influenza-like viruses. the peak occurrence of influenza-like virus detection was earlier than the peak detection of influenza virus. in the 2014/15 influenza season, significant differences in the percentage of positive samples were observed between the 5-9 and 10-14 age groups. During the 2013/14 influenza season, there was no statistically significant difference in the percentage of positive samples between the 15-25, 26-44, and 45-64 year old age groups. Conclusions. A new division of age groups allows more accurate assessment of the incidence of influenza and influenza-like illnesses and can assist health workers in preventing multiorgan influenza-related complications and deaths.

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Identification of Hemagglutinin Residues Responsible for H3N2 Antigenic Drift during the 2014–2015 Influenza Season

Cited by 178 publications

References 17 publications

Amino Acids in Hemagglutinin Antigenic Site B Determine Antigenic and Receptor Binding Differences between A(H3N2)v and Ancestral Seasonal H3N2 Influenza Viruses

Amino Acids in Hemagglutinin Antigenic Site B Determine Antigenic and Receptor Binding Differences between A(H3N2)v and Ancestral Seasonal H3N2 Influenza Viruses

A Pyrosequencing-Based Approach to High-Throughput Identification of Influenza A(H3N2) Virus Clades Harboring Antigenic Drift Variants

A comparative analysis of influenza virus infections in the 2013/2014 and 2014/2015 epidemic seasons in the reporting system, for different age groups in Poland

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