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      Molecular genomic characterization of tick- and human-derived severe fever with thrombocytopenia syndrome virus isolates from South Korea

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          Abstract

          Background

          Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV) from Bunyaviridae that is endemic in East Asia. However, the genetic and evolutionary characteristics shared between tick- and human-derived Korean SFTSV strains are still limited.

          Methodology/Principal findings

          In this study we identify, for the first time, the genome sequence of a tick ( Haemaphysalis longicornis)-derived Korean SFTSV strain (designated as KAGWT) and compare this virus with recent human SFTSV isolates to identify the genetic variations and relationships among SFTSV strains. The genome of the KAGWT strain is consistent with the described genome of other members of the genus Phlebovirus with 6,368 nucleotides (nt), 3,378 nt, and 1,746 nt in the Large (L), Medium (M) and Small (S) segments, respectively. Compared with other completely sequenced human-derived Korean SFTSV strains, the KAGWT strain had highest sequence identities at the nucleotide and deduced amino acid level in each segment with the KAGWH3 strain which was isolated from SFTS patient within the same region, although there is one unique amino acid substitution in the Gn protein (A66S). Phylogenetic analyses of complete genome sequences revealed that at least four different genotypes of SFTSV are co-circulating in South Korea, and that the tick- and human-derived Korean SFTSV strains (genotype B) are closely related to one another. Although we could not detect reassortant, which are commonly observed in segmented viruses, further large-scale surveillance and detailed genomic analysis studies are needed to better understand the molecular epidemiology, genetic diversity, and evolution of SFTSV.

          Conclusions/Significance

          Full-length sequence analysis revealed a clear association between the genetic origins of tick- and human-derived SFTSV strains. While the most prevalent Korean SFTSV is genotype B, at least four different genotypes of SFTSV strains are co-circulating in South Korea. These findings provide information regarding the molecular epidemiology, genetic diversity, and evolution of SFTSV in East Asia.

          Author summary

          Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV). During entomological surveillance of SFTSV infection in Korean ticks collected from SFTS outbreak areas, we isolated a single SFTSV strain which we designated KAGWT. In addition, we isolated three SFTSVs from human patients with typical SFTS symptoms. In this study, we report the genomic sequences of each of these isolates and compare the genetic and evolutionary characteristics between tick- and human-derived Korean SFTSV isolates. Genetic and phylogenetic analyses of these sequences revealed that the tick-derived Korean SFTSV strain is clustered into genotype B, the most prevalent genotype in South Korea, and was closely related to other SFTSV in the same group. Furthermore, our results show that at least four different genotypes of SFTSV strains are co-circulating in South Korea.

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          Most cited references15

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          Recombination in viruses: Mechanisms, methods of study, and evolutionary consequences

          Highlights • Recombination is very relevant in generating genetic variability in viral populations. • Viral recombination has important consequences for different areas of research. These include molecular biology, virology and evolutionary biology. It also impacts the daily practice of clinicians and public health officials. • Here we review three important aspects of viral recombination: (i) molecular mechanisms of model DNA- and RNA-viruses, (ii) methods for detection, characterization and quantification in viral populations, (iii) its impact on the evolutionary analysis of viral populations.
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            Severe Fever with Thrombocytopenia Syndrome Virus in Ticks Collected from Humans, South Korea, 2013

            We investigated the infection rate for severe fever with thrombocytopenia syndrome virus (SFTSV) among ticks collected from humans during May–October 2013 in South Korea. Haemaphysalis longicornis ticks have been considered the SFTSV vector. However, we detected the virus in H. longicornis, Amblyomma testudinarium, and Ixodes nipponensis ticks, indicating additional potential SFTSV vectors.
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              First Detection of Heartland Virus (Bunyaviridae: Phlebovirus) from Field Collected Arthropods

              Heartland virus (HRTV), the first pathogenic Phlebovirus (Family: Bunyaviridae) discovered in the United States, was recently described from two Missouri farmers. In 2012, we collected 56,428 ticks representing three species at 12 sites including both patients' farms. Amblyomma americanum and Dermacentor variabilis accounted for nearly all ticks collected. Ten pools composed of deplete nymphs of A. americanum collected at a patient farm and a nearby conservation area were reverse transcription-polymerase chain reaction positive, and eight pools yielded viable viruses. Sequence data from the nonstructural protein of the Small segment indicates that tick strains and human strains are very similar, ≥ 97.6% sequence identity. This is the first study to isolate HRTV from field-collected arthropods and to implicate ticks as potential vectors. Amblyomma americanum likely becomes infected by feeding on viremic hosts during the larval stage, and transmission to humans occurs during the spring and early summer when nymphs are abundant and actively host seeking.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                22 September 2017
                September 2017
                : 11
                : 9
                : e0005893
                Affiliations
                [1 ] Division of Arboviruses, National Research Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju-si, Republic of Korea
                [2 ] College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju-si, Republic of Korea
                National Institute of Infectious Disease, JAPAN
                Author notes

                The authors have declared that no competing interests exist.

                [¤a]

                Current address: Division of Emerging Infectious Disease and Vector Research, Center for Infectious Diseases Research, National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju-si, Republic of Korea

                [¤b]

                Current address: Division of Viral Diseases, Center for Laboratory Control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju-si, Republic of Korea

                Author information
                http://orcid.org/0000-0002-9519-0219
                Article
                PNTD-D-17-00706
                10.1371/journal.pntd.0005893
                5627960
                28937979
                52ad8773-2e26-4902-ad08-e06617946d31
                © 2017 Yun et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 10 May 2017
                : 22 August 2017
                Page count
                Figures: 4, Tables: 3, Pages: 15
                Funding
                This research was funded by intramural grants of the Korea National Research Institute of Health (grant numbers: 2014-ND53001 and 2017-NI53002-00) and a grant of the Korea Health Industry Development Institute (grant number: HI15C2817). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Research and analysis methods
                Database and informatics methods
                Bioinformatics
                Sequence analysis
                DNA sequence analysis
                Research and Analysis Methods
                Database and Informatics Methods
                Bioinformatics
                Sequence Analysis
                Biology and Life Sciences
                Evolutionary Biology
                Evolutionary Genetics
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Sequencing Techniques
                Nucleotide Sequencing
                Research and Analysis Methods
                Molecular Biology Techniques
                Sequencing Techniques
                Nucleotide Sequencing
                Biology and Life Sciences
                Evolutionary Biology
                Evolutionary Systematics
                Phylogenetics
                Phylogenetic Analysis
                Biology and Life Sciences
                Taxonomy
                Evolutionary Systematics
                Phylogenetics
                Phylogenetic Analysis
                Computer and Information Sciences
                Data Management
                Taxonomy
                Evolutionary Systematics
                Phylogenetics
                Phylogenetic Analysis
                Research and Analysis Methods
                Database and Informatics Methods
                Bioinformatics
                Sequence Analysis
                Sequence Alignment
                Biology and Life Sciences
                Genetics
                Human Genetics
                Research and Analysis Methods
                Database and Informatics Methods
                Bioinformatics
                Sequence Analysis
                Amino Acid Sequence Analysis
                Custom metadata
                vor-update-to-uncorrected-proof
                2017-10-04
                All relevant data are within the paper and its Supporting Information files, and deposited in the GenBank database with accession numbers KY273136-KY273138 and KY789433-KY789441.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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