scholarly journals Age-seroprevalence curves for the multi-strain structure of influenza A virus

2021 ◽  
Author(s):  
Dao Nguyen Vinh ◽  
Nguyen Thi Duy Nhat ◽  
Erwin de Bruin ◽  
Nguyen Ha Thao Vy ◽  
Tran Thi Nhu Thao ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Principal Components ◽  
Influenza A ◽  
Principal Component ◽  
Population Exposure ◽  
Human Antibody ◽  
Human Influenza ◽  
Serum Samples ◽  
Tropical Country ◽  
Data Set

AbstractThe relationship between age and seroprevalence provides the simplest and least expensive approach to computing the annual attack rate of an infectious disease. However, many pathogens circulate as multiple serologically distinct strains, with no single assay able to determine seropositivity or seronegativity to an entire clade or family of co-circulating pathogens. An approach is needed to describe population exposure to an antigenically variable group of pathogens without focusing on any particular strain or serotype in the group. In this study, we focus on the two-subtype multi-strain taxonomy of human influenza A virus. We describe a data set of 24,402 general-population serum samples collected in central and southern Vietnam between 2009 to 2015, and assayed for influenza HA1 antibodies to eleven different strains of human influenza A (both H3 and H1 subtypes). We find that a principal components decomposition of the data results in the first principal component PC1 being an appropriate surrogate for seroprevalence (or composite antibody titer) which can be further decomposed for H1 and H3 contribution to the serological profile. Using this approach, we are able to provide the first ELISA-based standardized measurements of serology to reconstruct population exposure history, which correlates well with known influenza epidemiology. Annual attack rates in Vietnam are estimated at 25.6% (95% CI: 24.1% – 27.1%) for H3 and 16.0% (95% CI: 14.7% – 17.3%) for H1, with some variation in location-specific attack rates. The remaining principal components act as descriptors of influenza history and sort the population by birth year. The novel contributions of this analysis are (1) the introduction of dimensionality reduction on human antibody profiles to construct an age-seroprevalence relationship for an antigenically variable pathogen, (2) an analysis of >24,000 individuals, using >260,000 serological data points in total, allowing us to construct age-seroprevalence relationships with the precision of modern big data studies, and (3) a description of long-term attack rates in a non-vaccinated setting showing the natural history of influenza A virus in a densely-populated tropical country.

scholarly journals Age-seroprevalence curves for the multi-strain structure of influenza A virus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dao Nguyen Vinh ◽  
Nguyen Thi Duy Nhat ◽  
Erwin de Bruin ◽  
Nguyen Ha Thao Vy ◽  
Tran Thi Nhu Thao ◽  
...  
Keyword(s):  
Principal Components ◽  
Attack Rate ◽  
Influenza A ◽  
Principal Component ◽  
Human Antibody ◽  
Birth Cohorts ◽  
Serum Samples ◽  
The Relationship ◽  
Subtype H1 ◽  
Variable Group

AbstractThe relationship between age and seroprevalence can be used to estimate the annual attack rate of an infectious disease. For pathogens with multiple serologically distinct strains, there is a need to describe composite exposure to an antigenically variable group of pathogens. In this study, we assay 24,402 general-population serum samples, collected in Vietnam between 2009 to 2015, for antibodies to eleven human influenza A strains. We report that a principal components decomposition of antibody titer data gives the first principal component as an appropriate surrogate for seroprevalence; this results in annual attack rate estimates of 25.6% (95% CI: 24.1% – 27.1%) for subtype H3 and 16.0% (95% CI: 14.7% – 17.3%) for subtype H1. The remaining principal components separate the strains by serological similarity and associate birth cohorts with their particular influenza histories. Our work shows that dimensionality reduction can be used on human antibody profiles to construct an age-seroprevalence relationship for antigenically variable pathogens.

scholarly journals Homologous Recombination Is Very Rare or Absent in Human Influenza A Virus

2008 ◽  
Vol 82 (10) ◽  
pp. 4807-4811 ◽  
Author(s):  
Maciej F. Boni ◽  
Yang Zhou ◽  
Jeffery K. Taubenberger ◽  
Edward C. Holmes
Keyword(s):  
Homologous Recombination ◽  
Influenza A Virus ◽  
Influenza A ◽  
Secondary Analysis ◽  
Nonparametric Test ◽  
Minor Role ◽  
Template Switching ◽  
Human Influenza ◽  
Data Set ◽  
Phylogenetic Incongruence

ABSTRACT To determine the extent of homologous recombination in human influenza A virus, we assembled a data set of 13,852 sequences representing all eight segments and both major circulating subtypes, H3N2 and H1N1. Using an exhaustive search and a nonparametric test for mosaic structure, we identified 315 sequences (∼2%) in five different RNA segments that, after a multiple-comparison correction, had statistically significant mosaic signals compatible with homologous recombination. Of these, only two contained recombinant regions of sufficient length (>100 nucleotides [nt]) that the occurrence of homologous recombination could be verified using phylogenetic methods, with the rest involving very short sequence regions (15 to 30 nt). Although this secondary analysis revealed patterns of phylogenetic incongruence compatible with the action of recombination, neither candidate recombinant was strongly supported. Given our inability to exclude the occurrence of mixed infection and template switching during amplification, laboratory artifacts provide an alternative and likely explanation for the occurrence of phylogenetic incongruence in these two cases. We therefore conclude that, if it occurs at all, homologous recombination plays only a very minor role in the evolution of human influenza A virus.

scholarly journals octoFLU: Automated Classification for the Evolutionary Origin of Influenza A Virus Gene Sequences Detected in U.S. Swine

2019 ◽  
Vol 8 (32) ◽  
Author(s):  
Jennifer Chang ◽  
Tavis K. Anderson ◽  
Michael A. Zeller ◽  
Phillip C. Gauger ◽  
Amy L. Vincent
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Antigenic Drift ◽  
Evolutionary Origin ◽  
Automated Classification ◽  
Gene Sequences ◽  
Influenza A Viruses ◽  
Query Gene ◽  
Data Set ◽  
Virus Gene

The diversity of the 8 genes of influenza A viruses (IAV) in swine reflects introductions from nonswine hosts and subsequent antigenic drift and shift. Here, we curated a data set and present a pipeline that assigns evolutionary lineage and genetic clade to query gene segments.

scholarly journals Cooperation between the Hemagglutinin of Avian Viruses and the Matrix Protein of Human Influenza A Viruses

2002 ◽  
Vol 76 (4) ◽  
pp. 1781-1786 ◽  
Author(s):  
Christoph Scholtissek ◽  
Jürgen Stech ◽  
Scott Krauss ◽  
Robert G. Webster
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Matrix Protein ◽  
Gene Products ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
M Gene ◽  
Human Virus ◽  
Ha Gene ◽  
M Proteins

ABSTRACT To analyze the compatibility of avian influenza A virus hemagglutinins (HAs) and human influenza A virus matrix (M) proteins M1 and M2, we doubly infected Madin-Darby canine kidney cells with amantadine (1-aminoadamantane hydrochloride)-resistant human viruses and amantadine-sensitive avian strains. By using antisera against the human virus HAs and amantadine, we selected reassortants containing the human virus M gene and the avian virus HA gene. In our system, high virus yields and large, well-defined plaques indicated that the avian HAs and the human M gene products could cooperate effectively; low virus yields and small, turbid plaques indicated that cooperation was poor. The M gene products are among the primary components that determine the species specificities of influenza A viruses. Therefore, our system also indicated whether the avian HA genes effectively reassorted into the genome and replaced the HA gene of the prevailing human influenza A viruses. Most of the avian HAs that we tested efficiently cooperated with the M gene products of the early human A/PR/8/34 (H1N1) virus; however, the avian HAs did not effectively cooperate with the most recently isolated human virus that we tested, A/Nanchang/933/95 (H3N2). Cooperation between the avian HAs and the M proteins of the human A/Singapore/57 (H2N2) virus was moderate. These results suggest that the currently prevailing human influenza A viruses might have lost their ability to undergo antigenic shift and therefore are unable to form new pandemic viruses that contain an avian HA, a finding that is of great interest for pandemic planning.

scholarly journals Decomposing the Apoptosis Pathway Into Biologically Interpretable Principal Components

2018 ◽  
Vol 17 ◽  
pp. 117693511877108 ◽  
Author(s):  
Min Wang ◽  
Steven M Kornblau ◽  
Kevin R Coombes
Keyword(s):  
Principal Components ◽  
Myeloid Leukemia ◽  
Principal Component ◽  
R Package ◽  
Biological Data ◽  
Data Sets ◽  
Proteomics Data ◽  
Data Set ◽  
Apoptosis Pathway ◽  
Biological Interpretation

Principal component analysis (PCA) is one of the most common techniques in the analysis of biological data sets, but applying PCA raises 2 challenges. First, one must determine the number of significant principal components (PCs). Second, because each PC is a linear combination of genes, it rarely has a biological interpretation. Existing methods to determine the number of PCs are either subjective or computationally extensive. We review several methods and describe a new R package, PCDimension, that implements additional methods, the most important being an algorithm that extends and automates a graphical Bayesian method. Using simulations, we compared the methods. Our newly automated procedure is competitive with the best methods when considering both accuracy and speed and is the most accurate when the number of objects is small compared with the number of attributes. We applied the method to a proteomics data set from patients with acute myeloid leukemia. Proteins in the apoptosis pathway could be explained using 6 PCs. By clustering the proteins in PC space, we were able to replace the PCs by 6 “biological components,” 3 of which could be immediately interpreted from the current literature. We expect this approach combining PCA with clustering to be widely applicable.

scholarly journals Divergent Human-Origin Influenza Viruses Detected in Australian Swine Populations

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Frank Y. K. Wong ◽  
Celeste Donato ◽  
Yi-Mo Deng ◽  
Don Teng ◽  
Naomi Komadina ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Human Origin ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Data Set ◽  
Antigenic Properties

ABSTRACTGlobal swine populations infected with influenza A viruses pose a persistent pandemic risk. With the exception of a few countries, our understanding of the genetic diversity of swine influenza viruses is limited, hampering control measures and pandemic risk assessment. Here we report the genomic characteristics and evolutionary history of influenza A viruses isolated in Australia from 2012 to 2016 from two geographically isolated swine populations in the states of Queensland and Western Australia. Phylogenetic analysis with an expansive human and swine influenza virus data set comprising >40,000 sequences sampled globally revealed evidence of the pervasive introduction and long-term establishment of gene segments derived from several human influenza viruses of past seasons, including the H1N1/1977, H1N1/1995, H3N2/1968, and H3N2/2003, and the H1N1 2009 pandemic (H1N1pdm09) influenza A viruses, and a genotype that contained gene segments derived from the past three pandemics (1968, reemerged 1977, and 2009). Of the six human-derived gene lineages, only one, comprising two viruses isolated in Queensland during 2012, was closely related to swine viruses detected from other regions, indicating a previously undetected circulation of Australian swine lineages for approximately 3 to 44 years. Although the date of introduction of these lineages into Australian swine populations could not be accurately ascertained, we found evidence of sustained transmission of two lineages in swine from 2012 to 2016. The continued detection of human-origin influenza virus lineages in swine over several decades with little or unpredictable antigenic drift indicates that isolated swine populations can act as antigenic archives of human influenza viruses, raising the risk of reemergence in humans when sufficient susceptible populations arise.IMPORTANCEWe describe the evolutionary origins and antigenic properties of influenza A viruses isolated from two separate Australian swine populations from 2012 to 2016, showing that these viruses are distinct from each other and from those isolated from swine globally. Whole-genome sequencing of virus isolates revealed a high genotypic diversity that had been generated exclusively through the introduction and establishment of human influenza viruses that circulated in past seasons. We detected six reassortants with gene segments derived from human H1N1/H1N1pdm09 and various human H3N2 viruses that circulated during various periods since 1968. We also found that these swine viruses were not related to swine viruses collected elsewhere, indicating independent circulation. The detection of unique lineages and genotypes in Australia suggests that isolated swine populations that are sufficiently large can sustain influenza virus for extensive periods; we show direct evidence of a sustained transmission for at least 4 years between 2012 and 2016.

scholarly journals Computational analysis of drug like candidates against Neuraminidase of Human Influenza A virus subtypes

2020 ◽  
Vol 18 ◽  
pp. 100284
Author(s):  
Gracy Fathima Selvaraj ◽  
Shanmugavel Piramanayagam ◽  
Velmurugan Devadasan ◽  
Sameer Hassan ◽  
Kaveri Krishnasamy ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Computational Analysis ◽  
Human Influenza

Physicochemical study of the influenza A virus M2 protein and aluminum salt adjuvant interaction as a vaccine candidate model

2019 ◽  
Vol 14 (8) ◽  
pp. 523-536
Author(s):  
Maryam Saleh ◽  
Jamileh Nowroozi ◽  
Fatemeh Fotouhi ◽  
Behrokh Farahmand
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Structural Changes ◽  
Vaccine Candidate ◽  
Human Influenza ◽  
M2 Protein ◽  
Physicochemical Methods ◽  
Α Helix ◽  
High Level ◽  
Β Sheet

Aim: The present study evaluated the structural changes resulting from the interaction between a recombinant influenza A virus M2 protein and aluminum hydroxide adjuvant to investigate the antigen for further immunological studies. Materials & methods: Membrane protein II was produced from the H1N1 subtype of human influenza A virus. The interaction between M2 protein and alum inum hydroxide adjuvant was evaluated by physicochemical techniques including scanning electron microscope, UV-Vis spectra, Fourier-transform infrared spectroscopy and circular dichroism spectroscopy. Results: Physicochemical methods showed high-level protein adsorption and accessibility to the effective parts of the protein. Conclusion: It was concluded that M2 protein secondary structural perturbations, including the α-helix-to-β-sheet transition, enhanced its mechanical properties toward adsorption.

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