Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses
TL;DR: Genotypic and potential phenotypic differences imply that the isolates causing this outbreak form two separate subclades, and diversity among isolates implies that the H7N9 virus has evolved into at least two different lineages.
About: This article is published in The Lancet.The article was published on 2013-06-01. It has received 529 citations till now. The article focuses on the topics: Influenza A virus & Evolution of influenza.
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TL;DR: It is shown that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions and subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7n7 lineage.
Abstract: A novel H7N9 influenza A virus first detected in March 2013 has since caused more than 130 human infections in China, resulting in 40 deaths. Preliminary analyses suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza viruses, and carries some amino acids associated with mammalian receptor binding, raising concerns of a new pandemic. However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully known. Using a combination of active surveillance, screening of virus archives, and evolutionary analyses, here we show that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at live poultry markets, which are thought to be the immediate source of human infections. Whether the H7N9 outbreak lineage has, or will, become enzootic in China and neighbouring regions requires further investigation. The discovery here of a related H7N7 influenza virus in chickens that has the ability to infect mammals experimentally, suggests that H7 viruses may pose threats beyond the current outbreak. The continuing prevalence of H7 viruses in poultry could lead to the generation of highly pathogenic variants and further sporadic human infections, with a continued risk of the virus acquiring human-to-human transmissibility.
420 citations
TL;DR: Structural and functional studies of the two major surface envelope proteins demonstrate that neither has canonical HA or NA functions found in influenza viruses, but potential genomic reassortments of such influenza-like viruses with canonical influenza viruses cannot be excluded at this point and should be assessed.
287 citations
TL;DR: It is relevant to highlight that recurrent dehydration is suggested in multiple studies, a condition that possibly could be exacerbated in some cases by other conditions, including the use of nonsteroidal anti-inflammatory agents.
285 citations
Cites background from "Origin and diversity of novel avian..."
...During the past decade, several new infectious diseases have emerged: for example, SARS (severe acute respiratory syndrome) and its related coronavirus,(1) the A H1/N1 human flu strand that was responsible for a 2009 pandemic,(2) and the bird flu strain H7N9 that recently infected humans in China and caused more than 30 deaths.(3) For some newly recognized diseases, there still is no effective prevention or treatment....
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TL;DR: The sex ratios in urban compared with rural cases are consistent with exposure to poultry driving the risk of infection--a higher risk in men was only recorded in urban areas but not in rural areas, and the increased risk for men was of a similar magnitude for H7N9 and H5N1.
281 citations
TL;DR: Over more than 10 y of cocirculation of multiple H9N2 genotypes, a “fittest” genotype emerged with changed antigenicity and improved adaptability in chickens that became predominant in vaccinated farm chickens in China and caused widespread outbreaks before the H7N9 virus emergence.
Abstract: The emergence of human infection with a novel H7N9 influenza virus in China raises a pandemic concern. Chicken H9N2 viruses provided all six of the novel reassortant’s internal genes. However, it is not fully understood how the prevalence and evolution of these H9N2 chicken viruses facilitated the genesis of the novel H7N9 viruses. Here we show that over more than 10 y of cocirculation of multiple H9N2 genotypes, a genotype (G57) emerged that had changed antigenicity and improved adaptability in chickens. It became predominant in vaccinated farm chickens in China, caused widespread outbreaks in 2010–2013 before the H7N9 viruses emerged in humans, and finally provided all of their internal genes to the novel H7N9 viruses. The prevalence and variation of H9N2 influenza virus in farmed poultry could provide an important early warning of the emergence of novel reassortants with pandemic potential.
267 citations
Cites background from "Origin and diversity of novel avian..."
...Jiangsu, Shanghai, and Zhejiang, the first provinces that experienced outbreaks of the novel H7N9 viruses on humans (1, 3), are ideally situated for the cocirculation of H9N2, H7, and N9 viruses....
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...Phylogenetic analysis suggests that the virus is a triple reassortant of H7, N9, and H9N2 avian influenza viruses (3, 4)....
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References
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TL;DR: UNLABELLED RAxML-VI-HPC (randomized axelerated maximum likelihood for high performance computing) is a sequential and parallel program for inference of large phylogenies with maximum likelihood (ML) that has been used to compute ML trees on two of the largest alignments to date.
Abstract: Summary: RAxML-VI-HPC (randomized axelerated maximum likelihood for high performance computing) is a sequential and parallel program for inference of large phylogenies with maximum likelihood (ML). Low-level technical optimizations, a modification of the search algorithm, and the use of the GTR+CAT approximation as replacement for GTR+Γ yield a program that is between 2.7 and 52 times faster than the previous version of RAxML. A large-scale performance comparison with GARLI, PHYML, IQPNNI and MrBayes on real data containing 1000 up to 6722 taxa shows that RAxML requires at least 5.6 times less main memory and yields better trees in similar times than the best competing program (GARLI) on datasets up to 2500 taxa. On datasets ≥4000 taxa it also runs 2--3 times faster than GARLI. RAxML has been parallelized with MPI to conduct parallel multiple bootstraps and inferences on distinct starting trees. The program has been used to compute ML trees on two of the largest alignments to date containing 25 057 (1463 bp) and 2182 (51 089 bp) taxa, respectively.
Availability: icwww.epfl.ch/~stamatak
Contact: Alexandros.Stamatakis@epfl.ch
Supplementary information: Supplementary data are available at Bioinformatics online.
14,847 citations
TL;DR: BEAST is a fast, flexible software architecture for Bayesian analysis of molecular sequences related by an evolutionary tree that provides models for DNA and protein sequence evolution, highly parametric coalescent analysis, relaxed clock phylogenetics, non-contemporaneous sequence data, statistical alignment and a wide range of options for prior distributions.
Abstract: The evolutionary analysis of molecular sequence variation is a statistical enterprise. This is reflected in the increased use of probabilistic models for phylogenetic inference, multiple sequence alignment, and molecular population genetics. Here we present BEAST: a fast, flexible software architecture for Bayesian analysis of molecular sequences related by an evolutionary tree. A large number of popular stochastic models of sequence evolution are provided and tree-based models suitable for both within- and between-species sequence data are implemented. BEAST version 1.4.6 consists of 81000 lines of Java source code, 779 classes and 81 packages. It provides models for DNA and protein sequence evolution, highly parametric coalescent analysis, relaxed clock phylogenetics, non-contemporaneous sequence data, statistical alignment and a wide range of options for prior distributions. BEAST source code is object-oriented, modular in design and freely available at http://beast-mcmc.googlecode.com/
under the GNU LGPL license. BEAST is a powerful and flexible evolutionary analysis package for molecular sequence variation. It also provides a resource for the further development of new models and statistical methods of evolutionary analysis.
11,916 citations
TL;DR: In this paper, the authors introduce a new approach to perform relaxed phylogenetic analysis, which can be used to estimate phylogenies and divergence times in the face of uncertainty in evolutionary rates and calibration times.
Abstract: In phylogenetics, the unrooted model of phylogeny and the strict molecular clock model are two extremes of a continuum. Despite their dominance in phylogenetic inference, it is evident that both are biologically unrealistic and that the real evolutionary process lies between these two extremes. Fortunately, intermediate models employing relaxed molecular clocks have been described. These models open the gate to a new field of “relaxed phylogenetics.” Here we introduce a new approach to performing relaxed phylogenetic analysis. We describe how it can be used to estimate phylogenies and divergence times in the face of uncertainty in evolutionary rates and calibration times. Our approach also provides a means for measuring the clocklikeness of datasets and comparing this measure between different genes and phylogenies. We find no significant rate autocorrelation among branches in three large datasets, suggesting that autocorrelated models are not necessarily suitable for these data. In addition, we place these datasets on the continuum of clocklikeness between a strict molecular clock and the alternative unrooted extreme. Finally, we present analyses of 102 bacterial, 106 yeast, 61 plant, 99 metazoan, and 500 primate alignments. From these we conclude that our method is phylogenetically more accurate and precise than the traditional unrooted model while adding the ability to infer a timescale to evolution.
5,812 citations
TL;DR: The fundamental equations of the general model, with 12 independent substitution parameters, are used to obtain a formula which corrects the effect of multiple and parallel substitutions on the measure of evolutionary divergence between two homologous sequences.
2,302 citations