scholarly journals Machine Learning Prediction and Experimental Validation of Antigenic Drift in H3 Influenza A Viruses in Swine

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Michael A. Zeller ◽  
Phillip C. Gauger ◽  
Zebulun W. Arendsee ◽  
Carine K. Souza ◽  
Amy L. Vincent ◽  
...  
Keyword(s):  
Public Health ◽  
Amino Acid ◽  
Regression Models ◽  
Influenza A ◽  
Sequence Data ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Genetic Sequence ◽  
Nonlinear Regression Models ◽  
Antigenic Phenotype

ABSTRACT The antigenic diversity of influenza A viruses (IAV) circulating in swine challenges the development of effective vaccines, increasing zoonotic threat and pandemic potential. High-throughput sequencing technologies can quantify IAV genetic diversity, but there are no accurate approaches to adequately describe antigenic phenotypes. This study evaluated an ensemble of nonlinear regression models to estimate virus phenotype from genotype. Regression models were trained with a phenotypic data set of pairwise hemagglutination inhibition (HI) assays, using genetic sequence identity and pairwise amino acid mutations as predictor features. The model identified amino acid identity, ranked the relative importance of mutations in the hemagglutinin (HA) protein, and demonstrated good prediction accuracy. Four previously untested IAV strains were selected to experimentally validate model predictions by HI assays. Errors between predicted and measured distances of uncharacterized strains were 0.35, 0.61, 1.69, and 0.13 antigenic units. These empirically trained regression models can be used to estimate antigenic distances between different strains of IAV in swine by using sequence data. By ranking the importance of mutations in the HA, we provide criteria for identifying antigenically advanced IAV strains that may not be controlled by existing vaccines and can inform strain updates to vaccines to better control this pathogen. IMPORTANCE Influenza A viruses (IAV) in swine constitute a major economic burden to an important global agricultural sector, impact food security, and are a public health threat. Despite significant improvement in surveillance for IAV in swine over the past 10 years, sequence data have not been integrated into a systematic vaccine strain selection process for predicting antigenic phenotype and identifying determinants of antigenic drift. To overcome this, we developed nonlinear regression models that predict antigenic phenotype from genetic sequence data by training the model on hemagglutination inhibition assay results. We used these models to predict antigenic phenotype for previously uncharacterized IAV, ranked the importance of genetic features for antigenic phenotype, and experimentally validated our predictions. Our model predicted virus antigenic characteristics from genetic sequence data and provides a rapid and accurate method linking genetic sequence data to antigenic characteristics. This approach also provides support for public health by identifying viruses that are antigenically advanced from strains used as pandemic preparedness candidate vaccine viruses.

scholarly journals Machine learning prediction and experimental validation of antigenic drift in H3 influenza A viruses in swine

2020 ◽  
Author(s):  
Michael A. Zeller ◽  
Phillip C. Gauger ◽  
Zebulun W. Arendsee ◽  
Carine K. Souza ◽  
Amy L. Vincent ◽  
...  
Keyword(s):  
Amino Acid ◽  
Regression Models ◽  
Influenza A ◽  
High Throughput Sequencing ◽  
Sequence Data ◽  
Antigenic Drift ◽  
Good Prediction ◽  
Linear Regression Models ◽  
Influenza A Viruses ◽  
Good Prediction Accuracy

ABSTRACTThe antigenic diversity of influenza A virus (IAV) circulating in swine challenges the development of effective vaccines, increasing zoonotic threat and pandemic potential. High throughput sequencing technologies are able to quantify IAV genetic diversity, but there are no accurate approaches to adequately describe antigenic phenotypes. This study evaluated an ensemble of non-linear regression models to estimate virus phenotype from genotype. Regression models were trained with a phenotypic dataset of pairwise hemagglutination inhibition (HI) assays, using genetic sequence identity and pairwise amino acid mutations as predictor features. The model identified amino acid identity, ranked the relative importance of mutations in the hemagglutinin (HA) protein, and demonstrated good prediction accuracy. Four previously untested IAV strains were selected to experimentally validate model predictions by HI assays. Error between predicted and measured distances of uncharacterized strains were 0.34, 0.70, 2.19, and 0.17 antigenic units. These empirically trained regression models can be used to estimate antigenic distances between different strains of IAV in swine using sequence data. By ranking the importance of mutations in the HA, we provide criteria for identifying antigenically advanced IAV strains that may not be controlled by existing vaccines and can inform strain updates to vaccines to better control this pathogen.

scholarly journals Genetic and Antigenic Evolution of European Swine Influenza A Viruses of HA-1C (Avian-Like) and HA-1B (Human-Like) Lineages in France from 2000 to 2018

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1304
Author(s):  
Amélie Chastagner ◽  
Séverine Hervé ◽  
Stéphane Quéguiner ◽  
Edouard Hirchaud ◽  
Pierrick Lucas ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Phylogenetic Analyses ◽  
Swine Influenza ◽  
Amino Acid Sequences ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Double Deletion ◽  
Antigenic Evolution ◽  
Amino Acid Mutations

This study evaluated the genetic and antigenic evolution of swine influenza A viruses (swIAV) of the two main enzootic H1 lineages, i.e., HA-1C (H1av) and -1B (H1hu), circulating in France between 2000 and 2018. SwIAV RNAs extracted from 1220 swine nasal swabs were hemagglutinin/neuraminidase (HA/NA) subtyped by RT-qPCRs, and 293 virus isolates were sequenced. In addition, 146 H1avNy and 105 H1huNy strains were submitted to hemagglutination inhibition tests. H1avN1 (66.5%) and H1huN2 (25.4%) subtypes were predominant. Most H1 strains belonged to HA-1C.2.1 or -1B.1.2.3 clades, but HA-1C.2, -1C.2.2, -1C.2.3, -1B.1.1, and -1B.1.2.1 clades were also detected sporadically. Within HA-1B.1.2.3 clade, a group of strains named “Δ146-147” harbored several amino acid mutations and a double deletion in HA, that led to a marked antigenic drift. Phylogenetic analyses revealed that internal segments belonged mainly to the “Eurasian avian-like lineage”, with two distinct genogroups for the M segment. In total, 17 distinct genotypes were identified within the study period. Reassortments of H1av/H1hu strains with H1N1pdm virus were rarely evidenced until 2018. Analysis of amino acid sequences predicted a variability in length of PB1-F2 and PA-X proteins and identified the appearance of several mutations in PB1, PB1-F2, PA, NP and NS1 proteins that could be linked to virulence, while markers for antiviral resistance were identified in N1 and N2. Altogether, diversity and evolution of swIAV recall the importance of disrupting the spreading of swIAV within and between pig herds, as well as IAV inter-species transmissions.

Optimization of M2e cassette amino acid composition for the development of universal influenza vaccine

2021 ◽  
Vol 21 (3) ◽  
pp. 127-130
Author(s):  
Daria А. Mezhenskaya ◽  
Irina N. Isakova-Sivak ◽  
Anastasiya E. Katelnikova ◽  
Larisa G. Rudenko
Keyword(s):  
Public Health ◽  
Amino Acid ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Wide Spectrum ◽  
Qualitative Assessment ◽  
Influenza A Viruses ◽  
Duration Of Action ◽  
Natural Reservoir ◽  
Universal Influenza Vaccine

The development of a universal influenza vaccine with a wide spectrum and duration of action is one of the serious public health problems. This study is dedicated to optimization of an immunogen covering the M2e epitopes of influenza A viruses circulating in the natural reservoir, as well as the creation of a prototype of a universal influenza vaccine with subsequent quantitative and qualitative assessment of the induced anti-M2e responses in ferrets.

scholarly journals Novel Swine Infl uenza AH1N1 and the Phase Six Pandemic

2010 ◽  
Vol 49 (179) ◽  
Author(s):  
M Khadka
Keyword(s):  
Public Health ◽  
Influenza A ◽  
Swine Influenza ◽  
Antigenic Drift ◽  
World Health ◽  
Health Concern ◽  
Influenza A Viruses ◽  
Influenza A H1n1 ◽  
H1n1 Strain ◽  
Health Organization

The family Orthomyxoviridae consists of Influenza A virus which is negative sense single stranded virus. The genome of the virus is segmented and possesses a peculiar trait of genetic reassortment. The influenza virus on its envelop consists of the antigenic glycoprotein like haemagglutinin (HA) and neuraminidase (NA). The changes in those glycoprotein components due to antigenic shift and antigenic drift leads to the development of new strain of Influenza A viruses. Now the novel swine influenza A/H1N1 strain has been detected from different parts of the world which is causing pandemic. World Health Organization has declared the pandemic phase six and more than 60 countries have reported the cases of novel influenza A/H1N1 strain including Nepal. As the disease is spreading world wide, it is a major public health concern for all the countries. And especially the developing countries like Nepal should immediately respond to the situation and should be well prepared to combat the disease before the disease spreads to enough population. Keywords: pandemic, public health, reassortment, swine influenza A/H1N1.

scholarly journals Antigenic drift in the evolution of H1N1 influenza A viruses resulting from deletion of a single amino acid in the haemagglutinin gene

2007 ◽  
Vol 88 (12) ◽  
pp. 3209-3213 ◽  
Author(s):  
Natalie J. McDonald ◽  
Catherine B. Smith ◽  
Nancy J. Cox
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Reverse Genetics ◽  
Selective Advantage ◽  
H1n1 Influenza ◽  
Antigenic Drift ◽  
Surface Glycoprotein ◽  
Single Amino Acid ◽  
Influenza A Viruses ◽  
Sequence Comparisons

Two genetically distinct lineages of H1N1 influenza A viruses, circulated worldwide before 1994, were antigenically indistinguishable. In 1994, viruses emerged in China, including A/Beijing/262/95, with profound antigenic differences from the contemporary circulating H1N1 strains. Haemagglutinin sequence comparisons of either a predecessor virus, A/Hebei/52/94, or one representative of the cocirculating A/Bayern/7/95-like clade, A/Shenzhen/227/95, revealed a deletion of K at position 134 (H3 numbering) in the antigenic variants. The K134 deletion conferred a selective advantage to the Chinese deletion lineage, such that it eventually gave rise to currently circulating H1 viruses. Using reverse genetics to generate viruses with either an insertion or deletion of aa 134, we have confirmed that the K134 deletion, rather than a constellation of sublineage specific amino acid changes, was sufficient for the antigenic difference observed in the Chinese deletion lineage, and reinsertion of K134 revealed the requirement of a compatible neuraminidase surface glycoprotein for viral growth.

scholarly journals Antigenic drift in influenza A viruses. I. Selection and characterization of antigenic variants of A/PR/8/34 [HON1] influenza virus with monoclonal antibodies

1978 ◽  
Vol 148 (2) ◽  
pp. 383-392 ◽  
Author(s):  
W Gerhard ◽  
RG Webster
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Amino Acid ◽  
Influenza A ◽  
Antigenic Drift ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Parent Virus ◽  
Influenza A Viruses

Antigenic variants of A/PR/8/34 [HON1] influenza virus were selected after a single passage of the parent virus in embryonated chicken eggs in the presence of monoclonal antibodies to this virus. The monoclonal antibodies were produced by a hybridoma and were specific for an antigenic determinant on the HA molecule of the parent virus. Seven antigenic variants were analyzed with 95 monoclonal anti-HA antibodies prepared in vitro in the splenic fragment culture system. Three subgroups of antigenic variants were distinguished. The antigenic changes were primarily recognized by monoclonal antibodies to the strain- specific determinants of the parental hemagglutinin (HA) molecule. Monoclonal antibodies to HA determinants shared (in an identical or cross-reactive form) by parental virus and more than three heterologous viruses of the HON1 and H1N1 subtypes were unable to recognize the antigenic change on the variants. Similarly, heterogeneous antibody preparations could not differentiate between parental and variant viruses. The results are compatible with the idea that the HA of PR8 has available a large repertoire of antigenic modifications that may result from single amino acid substitutions, and that antigenic changes can occur in the strain- specific determinants on the HA molecule in the absence of concomitant changes in the cross-reactive HA determinants. The findings suggest that antigenic drift, in order to be epidemiologically significant, probably requires a series of amino acid substitutions in, or close to, the antigenic area on the HA molecule.

scholarly journals Characterization of H9N2 influenza A viruses isolated from chicken products imported into Japan from China

2006 ◽  
Vol 135 (3) ◽  
pp. 386-391 ◽  
Author(s):  
M. MASE ◽  
M. ETO ◽  
K. IMAI ◽  
K. TSUKAMOTO ◽  
S. YAMAGUCHI
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Influenza A ◽  
H9n2 Virus ◽  
Amino Acid Substitutions ◽  
Influenza A Viruses ◽  
Potential Sources

We characterized eleven H9N2 influenza A viruses isolated from chicken products imported from China. Genetically they were classified into six distinct genotypes, including five already known genotypes and one novel genotype. This suggested that such multiple genotypes of the H9N2 virus have possibly already become widespread and endemic in China. Two isolates have amino-acid substitutions that confer resistance to amantadine in the M2 region, and this supported the evidence that this mutation might be a result of the wide application of amantadine for avian influenza treatment in China. These findings emphasize the importance of surveillance for avian influenza virus in this region, and of quarantining imported chicken products as potential sources for the introduction of influenza virus.

scholarly journals Molecular Characterization of Seasonal Influenza A and B from Hospitalized Patients in Thailand in 2018–2019

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 977
Author(s):  
Kobporn Boonnak ◽  
Chayasin Mansanguan ◽  
Dennis Schuerch ◽  
Usa Boonyuen ◽  
Hatairat Lerdsamran ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
Antigenic Drift ◽  
Influenza B ◽  
Receptor Binding Site ◽  
Antigenic Sites ◽  
Ha Protein

Influenza viruses continue to be a major public health threat due to the possible emergence of more virulent influenza virus strains resulting from dynamic changes in virus adaptability, consequent of functional mutations and antigenic drift in surface proteins, especially hemagglutinin (HA) and neuraminidase (NA). In this study, we describe the genetic and evolutionary characteristics of H1N1, H3N2, and influenza B strains detected in severe cases of seasonal influenza in Thailand from 2018 to 2019. We genetically characterized seven A/H1N1 isolates, seven A/H3N2 isolates, and six influenza B isolates. Five of the seven A/H1N1 viruses were found to belong to clade 6B.1 and were antigenically similar to A/Switzerland/3330/2017 (H1N1), whereas two isolates belonged to clade 6B.1A1 and clustered with A/Brisbane/02/2018 (H1N1). Interestingly, we observed additional mutations at antigenic sites (S91R, S181T, T202I) as well as a unique mutation at a receptor binding site (S200P). Three-dimensional (3D) protein structure analysis of hemagglutinin protein reveals that this unique mutation may lead to the altered binding of the HA protein to a sialic acid receptor. A/H3N2 isolates were found to belong to clade 3C.2a2 and 3C.2a1b, clustering with A/Switzerland/8060/2017 (H3N2) and A/South Australia/34/2019 (H3N2), respectively. Amino acid sequence analysis revealed 10 mutations at antigenic sites including T144A/I, T151K, Q213R, S214P, T176K, D69N, Q277R, N137K, N187K, and E78K/G. All influenza B isolates in this study belong to the Victoria lineage. Five out of six isolates belong to clade 1A3-DEL, which relate closely to B/Washington/02/2009, with one isolate lacking the three amino acid deletion on the HA segment at position K162, N163, and D164. In comparison to the B/Colorado/06/2017, which is the representative of influenza B Victoria lineage vaccine strain, these substitutions include G129D, G133R, K136E, and V180R for HA protein. Importantly, the susceptibility to oseltamivir of influenza B isolates, but not A/H1N1 and A/H3N2 isolates, were reduced as assessed by the phenotypic assay. This study demonstrates the importance of monitoring genetic variation in influenza viruses regarding how acquired mutations could be associated with an improved adaptability for efficient transmission.

scholarly journals Improving pandemic influenza risk assessment

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Colin A Russell ◽  
Peter M Kasson ◽  
Ruben O Donis ◽  
Steven Riley ◽  
John Dunbar ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Sequence Data ◽  
Virus Genome ◽  
Influenza Viruses ◽  
Influenza Surveillance ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Virus Genotype

Assessing the pandemic risk posed by specific non-human influenza A viruses is an important goal in public health research. As influenza virus genome sequencing becomes cheaper, faster, and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk assessment capabilities. However, the complexities of the relationships between virus genotype and phenotype make such predictions extremely difficult. The integration of experimental work, computational tool development, and analysis of evolutionary pathways, together with refinements to influenza surveillance, has the potential to transform our ability to assess the risks posed to humans by non-human influenza viruses and lead to improved pandemic preparedness and response.

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