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      Genomic Epidemiology, Evolution, and Transmission Dynamics of Porcine Deltacoronavirus

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          Abstract

          The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown once again that coronavirus (CoV) in animals are potential sources for epidemics in humans. Porcine deltacoronavirus (PDCoV) is an emerging enteropathogen of swine with a worldwide distribution. Here, we implemented and described an approach to analyze the epidemiology of PDCoV following its emergence in the pig population. We performed an integrated analysis of full genome sequence data from 21 newly sequenced viruses, along with comprehensive epidemiological surveillance data collected globally over the last 15 years. We found four distinct phylogenetic lineages of PDCoV, which differ in their geographic circulation patterns. Interestingly, we identified more frequent intra- and interlineage recombination and higher virus genetic diversity in the Chinese lineages compared with the USA lineage where pigs are raised in different farming systems and ecological environments. Most recombination breakpoints are located in the ORF1ab gene rather than in genes encoding structural proteins. We also identified five amino acids under positive selection in the spike protein suggesting a role for adaptive evolution. According to structural mapping, three positively selected sites are located in the N-terminal domain of the S1 subunit, which is the most likely involved in binding to a carbohydrate receptor, whereas the other two are located in or near the fusion peptide of the S2 subunit and thus might affect membrane fusion. Finally, our phylogeographic investigations highlighted notable South-North transmission as well as frequent long-distance dispersal events in China that could implicate human-mediated transmission. Our findings provide new insights into the evolution and dispersal of PDCoV that contribute to our understanding of the critical factors involved in CoVs emergence.

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

            A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
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              Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome

              The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. The novel coronavirus might have a role in causing SARS. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Contributors
                Role: Associate Editor
                Journal
                Mol Biol Evol
                Mol. Biol. Evol
                molbev
                Molecular Biology and Evolution
                Oxford University Press
                0737-4038
                1537-1719
                14 May 2020
                : msaa117
                Affiliations
                [m1 ] MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology, College of Veterinary Medicine, Nanjing Agricultural University , Nanjing, China
                [m2 ] Departments of Biomathematics and Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles , Los Angeles, CA
                [m3 ] Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles , Los Angeles, CA
                [m4 ] Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory for Clinical and Epidemiological Virology, KU Leuven , Leuven, Belgium
                [m5 ] Spatial Epidemiology Lab (SpELL), Université Libre de Bruxelles , Bruxelles, Belgium
                [m6 ] Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University , Hangzhou, China
                [m7 ] Institute for Virology, Center for Infection Medicine, Veterinary Faculty, Free University Berlin , Berlin, Germany
                [m8 ] Zhengzhou New Channel Agricultural Technology Co., Ltd, Zhengzhou , Henan, China
                [m9 ] Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University , Nanjing, Jiangsu, China
                Author notes

                Wan-Ting He, Xiang Ji, Wei He and Simon Dellicour contributed equally to this work.

                Corresponding author: E-mail: shuosu@ 123456njau.edu.cn .
                Present address: Department of Mathematics, Tulane University, New Orleans, LA
                Author information
                http://orcid.org/0000-0002-7243-0865
                Article
                msaa117
                10.1093/molbev/msaa117
                7454817
                32407507
                fbc20cc8-be76-4202-9f68-61eb6639f8f0
                © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

                This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                Page count
                Pages: 14
                Funding
                Funded by: National Natural Science Foundation of Outstanding Youth Fund in China;
                Award ID: 31922081
                Funded by: National Key Research and Development Program of China, DOI 10.13039/501100012166;
                Award ID: 2016YFD0500402
                Funded by: Fundamental Research Funds for the Central Universities, DOI 10.13039/501100012226;
                Award ID: Y0201900459
                Funded by: Six Talent Peaks Project of Jiangsu Province of China;
                Award ID: NY-045
                Funded by: Fonds National de la Recherche Scientifique;
                Funded by: National Institutes of Health, DOI 10.13039/100000002;
                Award ID: U19 AI135995
                Funded by: Interne Fondsen KU Leuven/Internal Funds KU Leuven;
                Award ID: C14/18/094
                Funded by: European Research Council under the European Union’s Horizon 2020;
                Award ID: 725422-ReservoirDOCS
                Funded by: Research Foundation—Flanders;
                Award ID: G066215N
                Award ID: G0D5117N
                Award ID: 75 G0B9317N
                Categories
                Article
                Custom metadata
                corrected-proof
                PAP

                Molecular biology
                porcine deltacoronavirus,evolution,recombination,phylogeographic,bayesian inference,beast

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