A captured viral interleukin 10 gene with cellular exon structure.

We have characterized a novel, captured and fully functional viral interleukin (IL)-10 homologue ((OvHV)IL-10) from the gammaherpesvirus ovine herpesvirus 2. Unlike IL-10 homologues from other gammaherpesviruses, the (OvHV)IL-10 peptide sequence was highly divergent from that of the host species. The (OvHV)IL-10 gene is unique amongst virus captured genes in that it has precisely retained the original cellular exon structure, having five exons of similar sizes to the cellular counterparts. However, the sizes of the introns are dramatically reduced. The (OvHV)IL-10 protein was shown to be a non-glycosylated, secreted protein of M(r) 21 000 with a signal peptidase cleavage site between amino acids 26 and 27 of the nascent peptide. Functional assays showed that (OvHV)IL-10, in a similar way to ovine IL-10, stimulated mast cell proliferation and inhibited macrophage inflammatory chemokine production. This is the first example of a captured herpesvirus gene retaining the full cellular gene structure.

[1]  Cedric Notredame,et al.  Computing Multiple Sequence/Structure Alignments with the T‐Coffee Package , 2003, Current protocols in bioinformatics.

[2]  D. McGeoch,et al.  Novel Mammalian Herpesviruses and Lineages within the Gammaherpesvirinae: Cospeciation and Interspecies Transfer , 2008, Journal of Virology.

[3]  Ziheng Yang.  PAML 4: phylogenetic analysis by maximum likelihood. , 2007, Molecular biology and evolution.

[4]  S. Brunak,et al.  Locating proteins in the cell using TargetP, SignalP and related tools , 2007, Nature Protocols.

[5]  J. Stewart,et al.  Complete sequence and analysis of the ovine herpesvirus 2 genome. , 2007, The Journal of general virology.

[6]  David R. Herndon,et al.  Comparison of ovine herpesvirus 2 genomes isolated from domestic sheep (Ovis aries) and a clinically affected cow (Bos bovis). , 2007, The Journal of general virology.

[7]  Andrew J Davison,et al.  Topics in herpesvirus genomics and evolution. , 2006, Virus research.

[8]  J. Stewart,et al.  Differential Transcription of Ovine Herpesvirus 2 Genes in Lymphocytes from Reservoir and Susceptible Species , 2006, Virus Genes.

[9]  K. Katoh,et al.  MAFFT version 5: improvement in accuracy of multiple sequence alignment , 2005, Nucleic acids research.

[10]  A. Rösen‐Wolff,et al.  The genome of equine herpesvirus type 2 harbors an interleukin 10 (IL10)-like gene , 1993, Virus Genes.

[11]  H. Kung,et al.  Retrotransposition and herpesvirus evolution , 2005, Virus Genes.

[12]  A. Bridgen,et al.  PCR detection of the sheep-associated agent of malignant catarrhal fever , 2005, Archives of Virology.

[13]  E. Holmes,et al.  The evolution of large DNA viruses: combining genomic information of viruses and their hosts. , 2004, Trends in microbiology.

[14]  Robert C. Edgar,et al.  MUSCLE: a multiple sequence alignment method with reduced time and space complexity , 2004, BMC Bioinformatics.

[15]  B. Slobedman,et al.  A Novel Viral Transcript with Homology to Human Interleukin-10 Is Expressed during Latent Human Cytomegalovirus Infection , 2004, Journal of Virology.

[16]  G. Darai,et al.  Poxvirus Homologues of Cellular Genes , 2004, Virus Genes.

[17]  John P. Huelsenbeck,et al.  MrBayes 3: Bayesian phylogenetic inference under mixed models , 2003, Bioinform..

[18]  A. Mercer,et al.  A comparison of the anti-inflammatory and immuno-stimulatory activities of orf virus and ovine interleukin-10. , 2002, Virus research.

[19]  Paul Kellam,et al.  Identification of new herpesvirus gene homologs in the human genome. , 2002, Genome research.

[20]  B. C. Jones,et al.  Noncompetitive antibody neutralization of IL-10 revealed by protein engineering and x-ray crystallography. , 2002, Structure.

[21]  Peter A. Barry,et al.  Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R1 , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[22]  A. Hughes.  Origin and Evolution of Viral Interleukin-10 and Other DNA Virus Genes with Vertebrate Homologues , 2002, Journal of Molecular Evolution.

[23]  N. Logsdon,et al.  Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site. , 2001, Immunity.

[24]  D. McGeoch,et al.  Molecular evolution of the Herpesvirinae , 2001 .

[25]  B. Lidbury,et al.  Genetic ‘budget’ of viruses and the cost to the infected host: A theory on the relationship between the genetic capacity of viruses, immune evasion, persistence and disease , 2001, Immunology and cell biology.

[26]  K. Lockridge,et al.  Primate cytomegaloviruses encode and express an IL-10-like protein. , 2000, Virology.

[27]  S. Pestka,et al.  Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10). , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[28]  S. Pestka,et al.  A Single Amino Acid Determines the Immunostimulatory Activity of Interleukin 10 , 2000, The Journal of experimental medicine.

[29]  Wood,et al.  Cytokine release by ovine macrophages following infection with Chlamydia psittaci , 1999, Clinical and experimental immunology.

[30]  D. McGeoch,et al.  The descent of human herpesvirus 8. , 1999, Seminars in cancer biology.

[31]  A. Ensser,et al.  Primary structure of the alcelaphine herpesvirus 1 genome , 1997, Journal of virology.

[32]  P. Hobart,et al.  Development of improved vectors for DNA-based immunization and other gene therapy applications. , 1997, Vaccine.

[33]  S. Menon,et al.  Crystal structure of Epstein-Barr virus protein BCRF1, a homolog of cellular interleukin-10. , 1997, Journal of molecular biology.

[34]  J. Stewart,et al.  Identification and characterization of murine gammaherpesvirus 68 gp150: a virion membrane glycoprotein , 1996, Journal of virology.

[35]  H. Reid,et al.  Cytolytic activity and associated serine protease expression by skin and afferent lymph CD8+ T cells during orf virus reinfection. , 1996, The Journal of general virology.

[36]  T. L. Nagabhushan,et al.  Crystal structure of interleukin 10 reveals an interferon gamma-like fold. , 1995, Biochemistry.

[37]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[38]  B. Fleischer,et al.  A sensitive and specific bioassay for the detection of human interleukin-10. , 1994, Journal of immunological methods.

[39]  T. Mosmann.  Properties and functions of interleukin-10. , 1994, Advances in immunology.

[40]  E. Kieff,et al.  Effects of virally expressed interleukin-10 on vaccinia virus infection in mice , 1993, Journal of virology.

[41]  J. Stewart,et al.  The interleukin-10 homolog encoded by Epstein-Barr virus enhances the reactivation of virus-specific cytotoxic T cell and HLA-unrestricted killer cell responses. , 1992, Virology.

[42]  M. Gulley,et al.  Epstein‐barr virus integration in human lymphomas and lymphoid cell lines , 1992, Cancer.

[43]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[44]  T. Mosmann,et al.  Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. , 1990, Science.

[45]  H. Reid,et al.  Malignant Catarrhal Fever and the Gammaherpesvirinae of Bovidae , 1989 .

[46]  J. Finlayson,et al.  Transmission of a malignant catarrhal fever-like syndrome to sheep: preliminary experiments. , 1985, Research in veterinary science.

[47]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[48]  E. Kieff,et al.  Chromosome site for Epstein-Barr virus DNA in a Burkitt tumor cell line and in lymphocytes growth-transformed in vitro. , 1983, Proceedings of the National Academy of Sciences of the United States of America.