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      Whole-genome analysis of coxsackievirus B3 reflects its genetic diversity in China and worldwide

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          Abstract

          Background

          Coxsackievirus B3 (CVB3) has emerged as an active pathogen in myocarditis, aseptic meningitis, hand, foot, and mouth disease (HFMD), and pancreatitis, and is a heavy burden on public health. However, CVB3 has not been systematically analyzed with regard to whole-genome diversity and recombination. Therefore, this study was undertaken to systematically examine the genetic characteristics of CVB3 based on its whole genome.

          Methods

          We combined CVB3 isolates from our national HFMD surveillance and global sequences retrieved from GenBank. Phylogenetic analysis was performed to examine the whole genome variety and recombination forms of CVB3 in China and worldwide.

          Results

          Phylogenetic analysis showed that CVB3 strains isolated worldwide could be classified into clusters A–E based on the sequence of the entire VP1 region. The predominant CVB3 strains in China belonged to cluster D, whereas cluster E CVB3 might be circulated globally compared to other clusters. The average nucleotide substitution rate in the P1 region of CVB3 was 4.82 × 10 –3 substitutions/site/year. Myocarditis was more common with cluster A. Clusters C and D presented more cases of acute flaccid paralysis, and cluster D may be more likely to cause HFMD. Multiple recombination events were detected among CVB3 variants, and there were twenty-three recombinant lineages of CVB3 circulating worldwide.

          Conclusions

          Overall, this study provides full-length genomic sequences of CVB3 isolates with a wide geographic distribution over a long-term time scale in China, which will be helpful for understanding the evolution of this pathogen. Simultaneously, continuous surveillance of CVB3 is indispensable to determine its genetic diversity in China as well as worldwide.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12985-022-01796-0.

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          Most cited references54

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          BEAST: Bayesian evolutionary analysis by sampling trees

          Background 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. Results 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 under the GNU LGPL license. Conclusion 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.
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            Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen)

            Gene sequences sampled at different points in time can be used to infer molecular phylogenies on a natural timescale of months or years, provided that the sequences in question undergo measurable amounts of evolutionary change between sampling times. Data sets with this property are termed heterochronous and have become increasingly common in several fields of biology, most notably the molecular epidemiology of rapidly evolving viruses. Here we introduce the cross-platform software tool, TempEst (formerly known as Path-O-Gen), for the visualization and analysis of temporally sampled sequence data. Given a molecular phylogeny and the dates of sampling for each sequence, TempEst uses an interactive regression approach to explore the association between genetic divergence through time and sampling dates. TempEst can be used to (1) assess whether there is sufficient temporal signal in the data to proceed with phylogenetic molecular clock analysis, and (2) identify sequences whose genetic divergence and sampling date are incongruent. Examination of the latter can help identify data quality problems, including errors in data annotation, sample contamination, sequence recombination, or alignment error. We recommend that all users of the molecular clock models implemented in BEAST first check their data using TempEst prior to analysis.
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              Identification of breakpoints in intergenotypic recombinants of HIV type 1 by bootscanning.

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                Author and article information

                Contributors
                yongzhang75@sina.com
                wenbo_xu1@aliyun.com
                Journal
                Virol J
                Virol J
                Virology Journal
                BioMed Central (London )
                1743-422X
                18 April 2022
                18 April 2022
                2022
                : 19
                : 69
                Affiliations
                [1 ]GRID grid.198530.6, ISNI 0000 0000 8803 2373, WHO WPRO Regional Polio Reference Laboratory, National Health Commission Key Laboratory for Medical Virology, National Institute for Viral Disease Control and Prevention, , Chinese Center for Disease Control and Prevention, ; 155 Changbai Road, Beijing, 102206 People’s Republic of China
                [2 ]GRID grid.9227.e, ISNI 0000000119573309, Center for Biosafety Mega-Science, , Chinese Academy of Sciences, ; Wuhan, 430071 People’s Republic of China
                [3 ]Shandong First Medical University & Shandong Academy of Medical Sciences, 619 Changcheng Road, Taian, 271016 People’s Republic of China
                Author information
                http://orcid.org/0000-0002-2692-5437
                Article
                1796
                10.1186/s12985-022-01796-0
                9014606
                35436962
                c1f3035e-167c-440b-a581-6cd83ed8dfd9
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 4 November 2021
                : 3 April 2022
                Funding
                Funded by: National Science and Technology Major Project of China
                Award ID: 2018ZX10305409-004-002
                Award Recipient :
                Funded by: National key research and development project
                Award ID: 2021YFC2302003
                Award ID: 2021YFC0863000
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Microbiology & Virology
                coxsackievirus b3 (cvb3),genome,recombination lineages,genetic diversity

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