Genetic and antigenic analysis of the first A/New Caledonia/20/99-like H1N1 influenza isolates reported in the Americas.
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SUBMITTER: Daum LT
PROVIDER: S-EPMC2730241 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Genome-wide gene expression patterns were measured in human monocyte-derived dendritic cells (DCs) infected in vitro with seasonal H1N1 influenza A/New Caledonia/20/1999. To provide a mechanistic explanation for the timing of gene expression changes over the first 12 hours post-infection, we developed a statistically rigorous enrichment approach integrating genome-wide expression kinetics and time-dependent promoter analysis. Our approach, TI me-Dependent Activity Linker (TIDAL), generates a regulatory network that connects transcription factors associated with each temporal phase of the response into a coherent linked cascade. TIDAL infers 12 transcription factors and 32 regulatory connections that drive the antiviral response to influenza. To demonstrate the generality of this approach, TIDAL was also used to generate a network for the DC response to measles infection.
2012-10-01 | GSE41067 | GEO
Project description:Genome-wide gene expression patterns were measured in human monocyte-derived dendritic cells (DCs) infected in vitro with seasonal H1N1 influenza A/New Caledonia/20/1999. To provide a mechanistic explanation for the timing of gene expression changes over the first 12 hours post-infection, we developed a statistically rigorous enrichment approach integrating genome-wide expression kinetics and time-dependent promoter analysis. Our approach, TI me-Dependent Activity Linker (TIDAL), generates a regulatory network that connects transcription factors associated with each temporal phase of the response into a coherent linked cascade. TIDAL infers 12 transcription factors and 32 regulatory connections that drive the antiviral response to influenza. To demonstrate the generality of this approach, TIDAL was also used to generate a network for the DC response to measles infection. Monocyte-derived DCs were obtained from healthy human blood donors following a standard protocol. The recent seasonal H1N1 influenza virus A/New Caledonia/20/1999 (NC) virus was titrated by immunofluorescence 18 hours after infection of MDCK cell plates using monoclonal antibodies specific for Influenza-NP protein generated by the Mount Sinai Hybridoma Core Facility followed by addition of anti-mouse IgG-FITC and visualization using fluorescent microscopy. For infection of naive DCs, NC stocks were appropriately diluted in DulbeccoM-bM-^@M-^Ys Modified Eagle Medium (DMEM) and added directly into pelleted DCs at a multiplicity of infection (MOI) of 1 After incubation for 40 minutes at 37 M-bM-^WM-&C, fresh DC growth medium (without GMCSF and IL-4) was added back to the infected cells (1 106 cells/ml) for the remainder of the infection. The reaction was stopped at 1, 2, 4, 6, 8, 10, and 12 hours after infection by fixing the cells with RNAprotect Cell Reagent (Qiagen, Duesseldorf Germany). Naive non-infected DCs underwent the same experimental procedure as infected DCs in the absence of virus to ensure that mechanical manipulations could not be responsible for differences in experimental readouts. All time points and controls were performed in triplicates. Cells were homogenized by using QIAshredder microcentrifuge spin-columns (Qiagen, Duesseldorf Germany) and RNA was isolated from cells using Qiagen Micro RNeasy plus kit following the manufactures protocol (Qiagen, Duesseldorf Germany). RNA quality was assayed by determination of the RNA integrity number using the 2100 Bioanalyzer (Agilent). RNA samples were processed and hybridized to HumanHT-12 v4 Expression BeadChip Kit (Illumina San Diego, CA) by the Mount Sinai Genomics Institute following the manufacturerM-bM-^@M-^Ys instructions, and raw expression data were output by the Illumina GenomeStudio software.
2012-10-01 | E-GEOD-41067 | biostudies-arrayexpress
Project description:Antigenic and genetic variations have been analyzed in eight consecutive isolates recovered from a child with severe combined immunodeficiency syndrome persistently infected with naturally acquired type A (H1N1) influenza virus over a 10-month period. Hemagglutination inhibition reactions and T1 oligonucleotide fingerprinting demonstrated that these viruses were related to strains causing outbreaks in the United States at that time (1983 to 1984) but that antigenic and genetic differences between consecutive isolates could be detected. This variation between isolates was examined further by sequencing the RNAs encoding the HA1 region of the hemagglutinin (HA) and the nucleoprotein (NP) in five of the consecutive isolates. Multiple point mutations were detected in both genes, and a deletion of one amino acid was detected in the HA. Depending on the isolates compared, 5.8 x 10(-3) to 17 x 10(-3) substitutions per nucleotide site per year were detected in the RNAs encoding the HA1, and 3.5 x 10(-3) to 24 x 10(-3) substitutions per nucleotide site per year were detected in the NP gene. Fifty-four percent of the base changes in the HA1 and 73% in the NP led to amino acid substitutions. A progressive accumulation of mutations over time was not observed, suggesting that the genetic diversity of these viruses may best be interpreted as the result of shifts in the population equilibrium (quasi-species) of replicating variant genomes.
| S-EPMC240585 | biostudies-other
Project description:The ease at which influenza virus sequence data can be used to estimate antigenic relationships between strains and the existence of databases containing sequence data for hundreds of thousands influenza strains make sequence-based antigenic distance estimates an attractive approach to researchers. Antigenic mismatch between circulating strains and vaccine strains results in significantly decreased vaccine effectiveness. Furthermore, antigenic relatedness between the vaccine strain and the strains an individual was originally primed with can affect the cross-reactivity of the antibody response. Thus, understanding the antigenic relationships between influenza viruses that have circulated is important to both vaccinologists and immunologists.Here we develop a method of mapping antigenic relationships between influenza virus stains using a sequence-based antigenic distance approach (SBM). We used a modified version of the p-all-epitope sequence-based antigenic distance calculation, which determines the antigenic relatedness between strains using influenza hemagglutinin (HA) genetic coding sequence data and provide experimental validation of the p-all-epitope calculation. We calculated the antigenic distance between 4838 H1N1 viruses isolated from infected humans between 1918 and 2016. We demonstrate, for the first time, that sequence-based antigenic distances of H1N1 Influenza viruses can be accurately represented in 2-dimenstional antigenic cartography using classic multidimensional scaling. Additionally, the model correctly predicted decreases in cross-reactive antibody levels with 87% accuracy and was highly reproducible with even when small numbers of sequences were used.This work provides a highly accurate and precise bioinformatics tool that can be used to assess immune risk as well as design optimized vaccination strategies. SBM accurately estimated the antigenic relationship between strains using HA sequence data. Antigenic maps of H1N1 virus strains reveal that strains cluster antigenically similar to what has been reported for H3N2 viruses. Furthermore, we demonstrated that genetic variation differs across antigenic sites and discuss the implications.
| S-EPMC5809904 | biostudies-other
Project description:BackgroundThere has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic.MethodsWe compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI).ResultsSince 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ?60 years, 45% of children aged 6-23 months, 32% of children aged 5-2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013-14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of their campaigns to April-May following the review of national evidence. LAC countries have also established an official network dedicated to evaluating influenza vaccines effectiveness and impact.ConclusionFollowing the A(H1N1)2009 influenza pandemic, countries of the Americas have continued their efforts to sustain or increase seasonal influenza vaccine uptake among high risk groups, especially among pregnant women. Countries also continued strengthening influenza surveillance, immunization platforms and information systems, indirectly improving preparedness for future pandemics. Influenza vaccination is particularly challenging compared to other vaccines included in EPI schedules, due to the need for annual, optimally timed vaccination, the wide spectrum of target groups, and the limitations of the available vaccines. Countries should continue to monitor influenza vaccination coverage, generate evidence for vaccination programs and implement social communication strategies addressing existing gaps.
| S-EPMC4994725 | biostudies-literature
Project description:BackgroundIn April 2009, novel swine-origin influenza viruses (S-OIV) were identified in patients from Mexico and the United States. The viruses were genetically characterized as a novel influenza A (H1N1) strain originating in swine, and within a very short time the S-OIV strain spread across the globe via human-to-human contact.MethodologyWe conducted a comprehensive computational search of all available sequences of the surface proteins of H1N1 swine influenza isolates and found that a similar strain to S-OIV appeared in Thailand in 2000. The earlier isolates caused infections in pigs but only one sequenced human case, A/Thailand/271/2005 (H1N1).SignificanceDifferences between the Thai cases and S-OIV may help shed light on the ability of the current outbreak strain to spread rapidly among humans.
| S-EPMC2712239 | biostudies-literature
Project description:Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis. Twenty one volunteers participated in an influenza challenge trial. We calculated the Daily Sum of Scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 hours post challenge was profiled on Illumina HT12v4 microarrays. We selected 19 genes with the largest fold change to train a random forest model with out of bag sampling cross validation. We observed good concordance between predicted and actual scores in an independent test set (overall Pearson correlation, r = 0.57; RMSE = -16.1%).
2017-06-10 | GSE90732 | GEO
Project description:The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control.
| S-EPMC4585932 | biostudies-literature
Project description:The pandemic influenza virus (2009 H1N1) was recently introduced into the human population. The hemagglutinin (HA) gene of 2009 H1N1 is derived from "classical swine H1N1" virus, which likely shares a common ancestor with the human H1N1 virus that caused the pandemic in 1918, whose descendant viruses are still circulating in the human population with highly altered antigenicity of HA. However, information on the structural basis to compare the HA antigenicity among 2009 H1N1, the 1918 pandemic, and seasonal human H1N1 viruses has been lacking. By homology modeling of the HA structure, here we show that HAs of 2009 H1N1 and the 1918 pandemic virus share a significant number of amino acid residues in known antigenic sites, suggesting the existence of common epitopes for neutralizing antibodies cross-reactive to both HAs. It was noted that the early human H1N1 viruses isolated in the 1930s-1940s still harbored some of the original epitopes that are also found in 2009 H1N1. Interestingly, while 2009 H1N1 HA lacks the multiple N-glycosylations that have been found to be associated with an antigenic change of the human H1N1 virus during the early epidemic of this virus, 2009 H1N1 HA still retains unique three-codon motifs, some of which became N-glycosylation sites via a single nucleotide mutation in the human H1N1 virus. We thus hypothesize that the 2009 H1N1 HA antigenic sites involving the conserved amino acids will soon be targeted by antibody-mediated selection pressure in humans. Indeed, amino acid substitutions predicted here are occurring in the recent 2009 H1N1 variants. The present study suggests that antibodies elicited by natural infection with the 1918 pandemic or its early descendant viruses play a role in specific immunity against 2009 H1N1, and provides an insight into future likely antigenic changes in the evolutionary process of 2009 H1N1 in the human population.
| S-EPMC2797400 | biostudies-literature
Project description:Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.
| S-EPMC3421718 | biostudies-literature