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      Novel Host-Related Virulence Factors Are Encoded by Squirrelpox Virus, the Main Causative Agent of Epidemic Disease in Red Squirrels in the UK

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          Abstract

          Squirrelpox virus (SQPV) shows little evidence for morbidity or mortality in North American grey squirrels ( Sciurus carolinensis), in which the virus is endemic. However, more recently the virus has emerged to cause epidemics with high mortality in Eurasian red squirrels ( S. vulgaris) in Great Britain, which are now threatened. Here we report the genome sequence of SQPV. Comparison with other Poxviridae revealed a core set of poxvirus genes, the phylogeny of which showed SQPV to be in a new Chordopoxvirus subfamily between the Molluscipoxviruses and Parapoxviruses. A number of SQPV genes were related to virulence, including three major histocomaptibility class I homologs, and one CD47 homolog. In addition, a novel potential virulence factor showing homology to mammalian oligoadenylate synthetase (OAS) was identified. This family of proteins normally causes activation of an endoribonuclease (RNaseL) within infected cells. The putative function of this novel SQPV protein was predicted in silico.

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          GeneMark.hmm: new solutions for gene finding.

          A. Lukashin (1998)
          The number of completely sequenced bacterial genomes has been growing fast. There are computer methods available for finding genes but yet there is a need for more accurate algorithms. The GeneMark. hmm algorithm presented here was designed to improve the gene prediction quality in terms of finding exact gene boundaries. The idea was to embed the GeneMark models into naturally derived hidden Markov model framework with gene boundaries modeled as transitions between hidden states. We also used the specially derived ribosome binding site pattern to refine predictions of translation initiation codons. The algorithm was evaluated on several test sets including 10 complete bacterial genomes. It was shown that the new algorithm is significantly more accurate than GeneMark in exact gene prediction. Interestingly, the high gene finding accuracy was observed even in the case when Markov models of order zero, one and two were used. We present the analysis of false positive and false negative predictions with the caution that these categories are not precisely defined if the public database annotation is used as a control.
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            Poxviruses and immune evasion.

            Alexandra Lucas, Joanna Sypula, Bruce T Seet … (2002)
            Large DNA viruses defend against hostile assault executed by the host immune system by producing an array of gene products that systematically sabotage key components of the inflammatory response. Poxviruses target many of the primary mediators of innate immunity including interferons, tumor necrosis factors, interleukins, complement, and chemokines. Poxviruses also manipulate a variety of intracellular signal transduction pathways such as the apoptotic response. Many of the poxvirus genes that disrupt these pathways have been hijacked directly from the host immune system, while others have demonstrated no clear resemblance to any known host genes. Nonetheless, the immunological targets and the diversity of strategies used by poxviruses to disrupt these host pathways have provided important insights into diverse aspects of immunology, virology, and inflammation. Furthermore, because of their anti-inflammatory nature, many of these poxvirus proteins hold promise as potential therapeutic agents for acute or chronic inflammatory conditions.
            Article 0 comments Cited 170 times – based on 0 reviews     Review now
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              Paired receptor specificity explained by structures of signal regulatory proteins alone and complexed with CD47.

              Deborah Hatherley, D. Stuart, Amy C. Graham … (2008)
              CD47 is a widely distributed cell-surface protein that acts a marker of self through interactions of myeloid and neural cells. We describe the high-resolution X-ray crystallographic structures of the immunoglobulin superfamily domain of CD47 alone and in complex with the N-terminal ligand-binding domain of signal regulatory protein alpha (SIRPalpha). The unusual and convoluted interacting face of CD47, comprising the N terminus and loops at the end of the domain, intercalates with the corresponding regions in SIRPalpha. We have also determined structures of the N-terminal domains of SIRPbeta, SIRPbeta(2), and SIRPgamma; proteins that are closely related to SIRPalpha but bind CD47 with negligible or reduced affinity. These results explain the specificity of CD47 for the SIRP family of paired receptors in atomic detail. Analysis of SIRPalpha polymorphisms suggests that these, as well as the activating SIRPs, may have evolved to counteract pathogen binding to the inhibitory SIRPalpha receptor.
              Article 0 comments Cited 78 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Xiangzhi Meng: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2014
                Publication date (Electronic): 1 July 2014
                Volume: 9
                Issue: 7
                Electronic Location Identifier: e96439
                Affiliations
                [1 ]University of Liverpool, Liverpool, United Kingdom
                [2 ]Moredun Research Institute, Penicuik, United Kingdom
                [3 ]University of Aarhus, Aarhus, Denmark
                [4 ]King Abdulaziz University, Jeddah, Saudi Arabia
                University of Texas HSC at San Antonio, United States of America
                Author notes

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

                Conceived and designed the experiments: ACD CJM ADR JC NH PMM. Performed the experiments: MH ARW KHK. Analyzed the data: NH ACD ADR CJM KHK. Contributed reagents/materials/analysis tools: CJM. Wrote the paper: CJM ACD AR NH JC.

                Article
                Publisher ID: PONE-D-13-01874
                DOI: 10.1371/journal.pone.0096439
                PMC ID: 4077651
                PubMed ID: 24983354
                SO-VID: 8470c073-78c6-4197-a581-eef92f5b74fc
                Copyright statement: Copyright @ 2014
                License:

                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
                Date received : 10 January 2013
                Date accepted : 8 April 2014
                Page count
                Pages: 7
                Funding
                We thank the Wildlife Ark Trust for their funding of this work, as part of their overall strategy to develop a vaccine against squirrel poxvirus. ACD was funded by the Royal College of Veterinary Surgeons trust. KHK and PMM were supported by the The Danish Council for Independent Research/Natural Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Biology and life sciences
                Subject: Computational Biology
                Subject: Comparative Genomics
                Subject: Evolutionary Biology
                Subject: Organismal Evolution
                Subject: Microbial Evolution
                Subject: Viral Evolution
                Subject: Genetics
                Subject: Genomics
                Subject: Immunology
                Subject: Immune Response
                Subject: Microbiology
                Subject: Virology
                Subject: Viral Classification
                Subject: Viral Transmission and Infection
                Subject: Molecular Biology
                Subject: Molecular Biology Techniques
                Subject: Sequencing Techniques
                Subject: Genome Sequencing
                Subject: Organisms
                Subject: Viruses
                Subject: DNA viruses
                Subject: Veterinary Science
                Subject: Veterinary Diseases
                Subject: Veterinary Virology
                Subject: Zoonoses
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Pathogenesis
                Subject: Host-Pathogen Interactions

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

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