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      Analysis and insights into recombination signals in lumpy skin disease virus recovered in the field

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          Abstract

          Wide spread incidences of vaccine-like strains of lumpy skin disease virus (LSDV) have recently been reported in a Russian region with a neighboring country that actively vaccinate with a live attenuated LSD vaccine. The use of live-attenuated viruses (LAVs) as vaccines during an active outbreak, creates potential ground for coinfection of hosts and emergence of a strain combining genetic fragments of both parental vaccine and field strains. In this study, we analyse the vaccine-like strain LSDV RUSSIA/Saratov/2017 detected in Saratovskaya oblast, a region sharing border with Kazakhstan. To gain insight into possible recombination signals, a full-genome next-generation sequencing of the viral genome was performed using the Illumina platform. The genome contains the backbone of a live-attenuated vaccine with a patchwork of wild-type field virus DNA fragments located throughout. A total of 27 recombination events were identified. The average distance between the recombination sites was 3400 base pairs (bp). The impact of the recombination events on the virulence and transmission capacity of the identified virus remains to be clarified. These findings provide evidence for the first time of genetic exchanges between closely related strains of capripoxviruses in the field and a vaccine strain, and prompt a revisiting of the vaccination issue for a safe and efficacious prevention and control strategy of LSD.

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          Most cited references32

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          Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination.

          The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, nef, and the 3' long terminal repeat as determined by both maximal chi2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.
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            Analyzing the mosaic structure of genes.

            Some genes in prokaryotes consist of a mosaic of regions derived from different ancestors by horizontal gene transfer. A method is described for demonstrating the statistical significance of such mosaic structure and for locating the crossover points separating different regions.
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              A modified bootscan algorithm for automated identification of recombinant sequences and recombination breakpoints.

              We have developed a modified BOOTSCAN algorithm that may be used to screen nucleotide sequence alignments for evidence of recombination without prior identification of nonrecombinant reference sequences. The algorithm is fast and includes a Bonferroni corrected statistical test of recombination to circumvent the multiple testing problems encountered when using the BOOTSCAN method to explore alignments for evidence of recombination. Using both simulated and real datasets we demonstrate that the modified algorithm is more powerful than other phylogenetic recombination detection methods and performs almost as well as one of the best substitution distribution recombination detection methods.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Investigation
                Role: Investigation
                Role: Data curationRole: Writing – review & editing
                Role: SoftwareRole: VisualizationRole: Writing – original draft
                Role: Supervision
                Role: Conceptualization
                Role: SupervisionRole: Writing – review & editing
                Role: Data curationRole: Funding acquisitionRole: Project administrationRole: Supervision
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 December 2018
                2018
                : 13
                : 12
                : e0207480
                Affiliations
                [1 ] Federal Center for Animal Health, Vladimir, Russia
                [2 ] Federal Budget Institution of Science "Central Research Institute of Epidemiology”, Moscow, Russia
                [3 ] ARC-Onderstepoort Veterinary Research institute, Onderstepoort, South Africa
                [4 ] Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa
                Oklahoma State University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-5982-3675
                Article
                PONE-D-18-24731
                10.1371/journal.pone.0207480
                6291113
                30540759
                c7e8168d-a76d-42b5-a74a-0f4dc45f8af9
                © 2018 Sprygin 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
                : 22 August 2018
                : 31 October 2018
                Page count
                Figures: 4, Tables: 2, Pages: 19
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Vaccines
                Recombinant Vaccines
                Biology and Life Sciences
                Genetics
                Genomics
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Vaccines
                Viral Vaccines
                Biology and Life Sciences
                Microbiology
                Virology
                Viral Vaccines
                Biology and life sciences
                Biochemistry
                Proteins
                DNA-binding proteins
                Biology and Life Sciences
                Genetics
                Genomics
                Microbial Genomics
                Viral Genomics
                Biology and Life Sciences
                Microbiology
                Microbial Genomics
                Viral Genomics
                Biology and Life Sciences
                Microbiology
                Virology
                Viral Genomics
                Biology and Life Sciences
                Biochemistry
                Proteins
                Recombinant Proteins
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Vaccines
                Biology and life sciences
                Genetics
                DNA
                DNA recombination
                Biology and life sciences
                Biochemistry
                Nucleic acids
                DNA
                DNA recombination
                Custom metadata
                The data underlying the results presented in the study are available from GenBank under accession number MH646674.

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                Uncategorized

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