1887

Abstract

Endotheliotropic elephant herpesvirus (elephantid herpesvirus 1; ElHV-1) is apathogenic for African elephants (), but causes fatal haemorrhagic disease in Asian elephants (). This is thought to occur through transmission from African elephants in places where both species are housed, such as zoological gardens. The virus has caused considerable losses in North American and European zoological gardens and thus severely impedes breeding of the endangered Asian elephant. Previously, the ultrastructural and genetic characterization of ElHV-1 from a male Asian elephant that died from the disease at the Berlin zoological gardens in 1998 have been reported. Here, a partial characterization of the ElHV-1 genome is presented. A 60 kbp locus, spanning 34 open reading frames, was analysed. Most of the detected genes were found to be conserved among the herpesviruses and showed an overall arrangement most similar to that of betaherpesviruses, in particular and . Most importantly, in addition to a protein kinase gene that is homologous to the human cytomegalovirus UL97 gene, a thymidine kinase (TK) gene was found, which is generally missing in betaherpesvirus genomes. Thus, ElHV-1 is the only known betaherpesvirus to encode a TK gene. This peculiarity might contribute to the fulminant pathogenicity of ElHV-1, but also provide a crucial enzymic activity for developing an efficient antiviral therapy with currently available nucleoside analogues.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81977-0
2006-10-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/10/2781.html?itemId=/content/journal/jgv/10.1099/vir.0.81977-0&mimeType=html&fmt=ahah

References

  1. Albini S., Zimmermann W., Neff F., Ehlers B., Häni H., Li H., Hüssy D., Engels M., Ackermann M. 2003; Identification and quantification of ovine gammaherpesvirus 2 DNA in fresh and stored tissues of pigs with symptoms of porcine malignant catarrhal fever. J Clin Microbiol 41:900–904 [CrossRef]
    [Google Scholar]
  2. Bennett M. S., Wien F., Champness J. N., Batuwangala T., Rutherford T., Summers W. C., Sun H., Wright G., Sanderson M. R. 1999; Structure to 1.9 Å resolution of a complex with herpes simplex virus type-1 thymidine kinase of a novel, non-substrate inhibitor: X-ray crystallographic comparison with binding of aciclovir. FEBS Lett 443:121–125 [CrossRef]
    [Google Scholar]
  3. Besser J., Sommer M. H., Zerboni L., Bagowski C. P., Ito H., Moffat J., Ku C.-C., Arvin A. M. 2003; Differentiation of varicella-zoster virus ORF47 protein kinase and IE62 protein binding domains and their contributions to replication in human skin xenografts in the SCID-hu mouse. J Virol 77:5964–5974 [CrossRef]
    [Google Scholar]
  4. Burkhardt S., Hentschke J., Weiler H., Ehlers B., Ochs A., Walter J., Wittstatt U., Göltenboth R. 1999; Elephant herpesvirus – a problem for breeding and housing of elephants. Berl Munch Tierarztl Wochenschr 112:174–179 (in German
    [Google Scholar]
  5. Chee M. S., Bankier A. T., Beck S. & 12 other authors 1990; Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr Top Microbiol Immunol 154:125–169
    [Google Scholar]
  6. Coen D. M., Kosz-Vnenchak M., Jacobson J. G., Leib D. A., Bogard C. L., Schaffer P. A., Tyler K. L., Knipe D. M. 1989; Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate. Proc Natl Acad Sci U S A 86:4736–4740 [CrossRef]
    [Google Scholar]
  7. Coleman H. M., de Lima B., Morton V., Stevenson P. G. 2003; Murine gammaherpesvirus 68 lacking thymidine kinase shows severe attenuation of lytic cycle replication in vivo but still establishes latency. J Virol 77:2410–2417 [CrossRef]
    [Google Scholar]
  8. Davison A. J., Stow N. D. 2005; New genes from old: redeployment of dUTPase by herpesviruses. J Virol 79:12880–12892 [CrossRef]
    [Google Scholar]
  9. Davison A. J., Dolan A., Akter P., Addison C., Dargan D. J., Alcendor D. J., McGeoch D. J., Hayward G. S. 2003; The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome. J Gen Virol 84:17–28 [CrossRef]
    [Google Scholar]
  10. Devereux J., Haeberli P., Smithies O. 1984; A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res 12:387–395 [CrossRef]
    [Google Scholar]
  11. Dolan A., Cunningham C., Hector R. D. & 12 other authors 2004; Genetic content of wild-type human cytomegalovirus. J Gen Virol 85:1301–1312 [CrossRef]
    [Google Scholar]
  12. Dominguez G., Dambaugh T. R., Stamey F. R., Dewhurst S., Inoue N., Pellett P. E. 1999; Human herpesvirus 6B genome sequence: coding content and comparison with human herpesvirus 6A. J Virol 73:8040–8052
    [Google Scholar]
  13. Dunn W., Chou C., Li H., Hai R., Patterson D., Stolc V., Zhu H., Liu F. 2003; Functional profiling of a human cytomegalovirus genome. Proc Natl Acad Sci U S A 100:14223–14228 [CrossRef]
    [Google Scholar]
  14. Edelman A. M., Blumenthal D. K., Krebs E. G. 1987; Protein serine/threonine kinases. Annu Rev Biochem 56:567–613 [CrossRef]
    [Google Scholar]
  15. Ehlers B., Burkhardt S., Goltz M., Bergmann V., Ochs A., Weiler H., Hentschke J. 2001; Genetic and ultrastructural characterization of a European isolate of the fatal endotheliotropic elephant herpesvirus. J Gen Virol 82:475–482
    [Google Scholar]
  16. Gompels U. A., Nicholas J., Lawrence G., Jones M., Thomson B. J., Martin M. E. D., Efstathiou S., Craxton M., Macaulay H. A. 1995; The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution. Virology 209:29–51 [CrossRef]
    [Google Scholar]
  17. Grose C., Tyler S., Peters G., Hiebert J., Stephens G. M., Ruyechan W. T., Jackson W., Storlie J., Tipples G. A. 2004; Complete DNA sequence analyses of the first two varicella-zoster virus glycoprotein E (D150N) mutant viruses found in North America: evolution of genotypes with an accelerated cell spread phenotype. J Virol 78:6799–6807 [CrossRef]
    [Google Scholar]
  18. Han M. G., Kweon C. H., Mo I. P., Kim S. J. 2002; Pathogenicity and vaccine efficacy of a thymidine kinase gene deleted infectious laryngotracheitis virus expressing the green fluorescent protein gene. Arch Virol 147:1017–1031 [CrossRef]
    [Google Scholar]
  19. Hanks S. K., Hunter T. 1995; Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J 9:576–596
    [Google Scholar]
  20. Hanks S. K., Quinn A. M., Hunter T. 1988; The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241:42–52 [CrossRef]
    [Google Scholar]
  21. Honess R. W., Gompels U. A., Barrell B. G., Craxton M., Cameron K. R., Staden R., Chang Y.-N., Hayward G. S. 1989; Deviations from expected frequencies of CpG dinucleotides in herpesvirus DNAs may be diagnostic of differences in the states of their latent genomes. J Gen Virol 70:837–855 [CrossRef]
    [Google Scholar]
  22. Hu H., Cohen J. I. 2005; Varicella-zoster virus open reading frame 47 (ORF47) protein is critical for virus replication in dendritic cells and for spread to other cells. Virology 337:304–311 [CrossRef]
    [Google Scholar]
  23. Huber M. T., Compton T. 1998; The human cytomegalovirus UL74 gene encodes the third component of the glycoprotein H-glycoprotein L-containing envelope complex. J Virol 72:8191–8197
    [Google Scholar]
  24. Kaashoek M. J., van Engelenburg F. A., Moerman A., Gielkens A. L., Rijsewijk F. A., van Oirschot J. T. 1996; Virulence and immunogenicity in calves of thymidine kinase- and glycoprotein E-negative bovine herpesvirus 1 mutants. Vet Microbiol 48:143–153 [CrossRef]
    [Google Scholar]
  25. Marschall M., Stein-Gerlach M., Freitag M., Kupfer R., van den Bogaard M., Stamminger T. 2002; Direct targeting of human cytomegalovirus protein kinase pUL97 by kinase inhibitors is a novel principle for antiviral therapy. J Gen Virol 83:1013–1023
    [Google Scholar]
  26. Marschall M., Marzi A., aus dem Siepen P., Jochmann R., Kalmer M., Auerochs S., Lischka P., Leis M., Stamminger T. 2005; Cellular p32 recruits cytomegalovirus kinase pUL97 to redistribute the nuclear lamina. J Biol Chem 280:33357–33367 [CrossRef]
    [Google Scholar]
  27. Masse M. J. O., Messerle M., Mocarski E. S. 1997; The location and sequence composition of the murine cytomegalovirus replicator ( ori Lyt. Virology 230:350–360 [CrossRef]
    [Google Scholar]
  28. Matte A., Tari L. W., Delbaere L. T. 1998; How do kinases transfer phosphoryl groups?. Structure 6:413–419 [CrossRef]
    [Google Scholar]
  29. Mätz-Rensing K., Jentsch K. D., Rensing S., Langenhuyzen S., Verschoor E., Niphuis H., Kaup F.-J. 2003; Fatal Herpes simplex infection in a group of common marmosets ( Callithrix jacchus . Vet Pathol 40:405–411 [CrossRef]
    [Google Scholar]
  30. McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., Taylor P. 1988; The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol 69:1531–1574 [CrossRef]
    [Google Scholar]
  31. McGeoch D. J., Rixon F. J., Davison A. J. 2006; Topics in herpesvirus genomics and evolution. Virus Res 117:90–104 [CrossRef]
    [Google Scholar]
  32. Mettenleiter T. C. 2000; Aujeszky's disease (pseudorabies) virus: the virus and molecular pathogenesis – state of the art; June 1999 Vet Res 31:99–115
    [Google Scholar]
  33. Michel D., Mertens T. 2004; The UL97 protein kinase of human cytomegalovirus and homologues in other herpesviruses: impact on virus and host. Biochim Biophys Acta 1697169–180 [CrossRef]
    [Google Scholar]
  34. Murphy E., Rigoutsos I., Shibuya T., Shenk T. E. 2003a; Reevaluation of human cytomegalovirus coding potential. Proc Natl Acad Sci U S A 100:13585–13590 [CrossRef]
    [Google Scholar]
  35. Murphy E., Yu D., Grimwood J. & 7 other authors 2003b; Coding potential of laboratory and clinical strains of human cytomegalovirus. Proc Natl Acad Sci U S A 100:14976–14981 [CrossRef]
    [Google Scholar]
  36. Ng T. I., Keenan L., Kinchington P. R., Grose C. 1994; Phosphorylation of varicella-zoster virus open reading frame (ORF) 62 regulatory product by viral ORF 47-associated protein kinase. J Virol 68:1350–1359
    [Google Scholar]
  37. Ossent P., Guscetti F., Metzler A. E., Lang E. M., Rubel A., Hauser B. 1990; Acute and fatal herpesvirus infection in a young Asian elephant ( Elephas maximus ). Vet Pathol 27:131–133 [CrossRef]
    [Google Scholar]
  38. Pevarello P., Brasca M. G., Amici R. & 27 other authors 2004; 3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor agents. J Med Chem 47:3367–3380 [CrossRef]
    [Google Scholar]
  39. Prichard M. N., Gao N., Jairath S., Mulamba G., Krosky P., Coen D. M., Parker B. O., Pari G. S. 1999; A recombinant human cytomegalovirus with a large deletion in UL97 has a severe replication deficiency. J Virol 73:5663–5670
    [Google Scholar]
  40. Prichard M. N., Williams A. D., Keith K. A., Harden E. A., Kern E. R. 2006; Distinct thymidine kinases encoded by cowpox virus and herpes simplex virus contribute significantly to the differential antiviral activity of nucleoside analogs. Antiviral Res 71:1–6 [CrossRef]
    [Google Scholar]
  41. Purves F. C., Ogle W. O., Roizman B. 1993; Processing of the herpes simplex virus regulatory protein α 22 mediated by the UL13 protein kinase determines the accumulation of a subset of α and γ mRNAs and proteins in infected cells. Proc Natl Acad Sci U S A 90:6701–6705 [CrossRef]
    [Google Scholar]
  42. Reid H. W., Buxton D., Berrie E., Pow I., Finlayson J. 1984; Malignant catarrhal fever. Vet Rec 114:581–583 [CrossRef]
    [Google Scholar]
  43. Richman L. K., Montali R. J., Garber R. L. 7 other authors 1999; Novel endotheliotropic herpesviruses fatal for Asian and African elephants. Science 283:1171–1176 [CrossRef]
    [Google Scholar]
  44. Saraste M., Sibbald P. R., Wittinghofer A. 1990; The P-loop – a common motif in ATP- and GTP-binding proteins. Trends Biochem Sci 15:430–434 [CrossRef]
    [Google Scholar]
  45. Schmitt D. L., Hardy D. A., Montali R. J., Richman L. K., Lindsay W. A., Isaza R., West G. 2000; Use of famciclovir for the treatment of endotheliotrophic herpesvirus infections in Asian elephants ( Elephas maximus ). J Zoo Wildl Med 31:518–522 [CrossRef]
    [Google Scholar]
  46. Siebert P. D., Chenchik A., Kellogg D. E., Lukyanov K. A., Lukyanov S. A. 1995; An improved PCR method for walking in uncloned genomic DNA. Nucleic Acids Res 23:1087–1088 [CrossRef]
    [Google Scholar]
  47. Slater J. D., Gibson J. S., Field H. J. 1993; Pathogenicity of a thymidine kinase-deficient mutant of equine herpesvirus 1 in mice and specific pathogen-free foals. J Gen Virol 74:819–828 [CrossRef]
    [Google Scholar]
  48. Talarico C. L., Burnette T. C., Miller W. H. & 8 other authors 1999; Acyclovir is phosphorylated by the human cytomegalovirus UL97 protein. Antimicrob Agents Chemother 43:1941–1946
    [Google Scholar]
  49. Ulrich S., Goltz M., Ehlers B. 1999; Characterization of the DNA polymerase loci of the novel porcine lymphotropic herpesviruses 1 and 2 in domestic and feral pigs. J Gen Virol 80:3199–3205
    [Google Scholar]
  50. Vink C., Beuken E., Bruggeman C. A. 1997; Cloning and functional characterization of the origin of lytic-phase DNA replication of rat cytomegalovirus. J Gen Virol 78:2963–2973
    [Google Scholar]
  51. Wagner M. J., Sharp J. A., Summers W. C. 1981; Nucleotide sequence of the thymidine kinase gene of herpes simplex virus type 1. Proc Natl Acad Sci U S A 78:1441–1445 [CrossRef]
    [Google Scholar]
  52. Whitley R. J., Hilliard J. K. 2001; Cercopithecine herpesvirus (B virus. In Fields Virology , 4th edn. pp  2835–2848 Edited by Knipe D. M., Howley P. M. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  53. Wu C.-C., Hsu T.-Y., Chen J.-Y. 2005; Characterization of three essential residues in the conserved ATP-binding region of Epstein-Barr virus thymidine kinase. Biochemistry 44:4785–4793 [CrossRef]
    [Google Scholar]
  54. Yokoyama N., Maeda K., Tohya Y., Kawaguchi Y., Shin Y.-S., Ono M., Ishiguro S., Fujikawa Y., Mikami T. 1996; Pathogenicity and vaccine efficacy of a thymidine kinase-deficient mutant of feline herpesvirus type 1 in cats. Arch Virol 141:481–494 [CrossRef]
    [Google Scholar]
  55. Yu D., Silva M. C., Shenk T. 2003; Functional map of human cytomegalovirus AD169 defined by global mutational analysis. Proc Natl Acad Sci U S A 100:12396–12401 [CrossRef]
    [Google Scholar]
  56. Zhang H. G., Hanson L. A. 1995; Deletion of thymidine kinase gene attenuates channel catfish herpesvirus while maintaining infectivity. Virology 209:658–663 [CrossRef]
    [Google Scholar]
  57. Zimmermann A., Michel D., Pavic I., Hampl W., Lüske A., Neyts J., De Clercq E., Mertens T. 1997; Phosphorylation of aciclovir, ganciclovir, penciclovir and S2242 by the cytomegalovirus UL97 protein: a quantitative analysis using recombinant vaccinia viruses. Antiviral Res 36:35–42 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81977-0
Loading
/content/journal/jgv/10.1099/vir.0.81977-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error