1887

Journal of General Virology header logo

Volume 88, Issue 12

The A5 gene of alcelaphine herpesvirus 1 encodes a constitutively active G-protein-coupled receptor that is non-essential for the induction of malignant catarrhal fever in rabbits Free

Abstract

Many gammaherpesviruses encode G-protein-coupled receptors (GPCRs). Several studies have revealed that gammaherpesvirus GPCRs are important for viral replication and for virus-induced pathogenesis. The gammaherpesvirus alcelaphine herpesvirus 1 (AlHV-1) is carried asymptomatically by wildebeest, but causes malignant catarrhal fever (MCF) following cross-species transmission to a variety of susceptible species. The A5 ORF of the AlHV-1 genome encodes a putative GPCR. In the present study, we investigated whether A5 encodes a functional GPCR and addressed its role in viral replication and in the pathogenesis of MCF. analysis supported the hypothesis that A5 could encode a functional GPCR as its expression product contained several hallmark features of GPCRs. Expression of A5 as tagged proteins in various cell lines revealed that A5 localizes in cell membranes, including the plasma membrane. Using [S]GTPS and reporter gene assays, we found that A5 is able to constitutively couple to -type G-proteins in transfected cells, and that this interaction is able to inhibit forskolin-triggered cAMP response element-binding protein (CREB) activation. Finally, using an AlHV-1 BAC clone, we produced a strain deleted for A5 and a revertant strain. Interestingly, the strain deleted for A5 replicated comparably to the wild-type parental strain and induced MCF in rabbits that was indistinguishable from that of the parental strain. The present study is the first to investigate the role of an individual gene of AlHV-1 in MCF pathogenesis.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83153-0
2007-12-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/12/3224.html?itemId=/content/journal/jgv/10.1099/vir.0.83153-0&mimeType=html&fmt=ahah

References

  1. Arvanitakis L., Geras-Raaka E., Varma A., Gershengorn M. C., Cesarman E. 1997; Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation. Nature 385:347–350 [CrossRef]
     [Google Scholar]
  2. Bais C., Santomasso B., Coso O., Arvanitakis L., Raaka E. G., Gutkind J. S., Asch A. S., Cesarman E., Gershengorn M. C. other authors 1998; G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator. Nature 391:86–89 [CrossRef]
     [Google Scholar]
  3. Bechtel J. T., Winant R. C., Ganem D. 2005; Host and viral proteins in the virion of Kaposi's sarcoma-associated herpesvirus. J Virol 79:4952–4964 [CrossRef]
     [Google Scholar]
  4. Beisser P. S., Verzijl D., Gruijthuijsen Y. K., Beuken E., Smit M. J., Leurs R., Bruggeman C. A., Vink C. 2005; The Epstein-Barr virus BILF1 gene encodes a G protein-coupled receptor that inhibits phosphorylation of RNA-dependent protein kinase. J Virol 79:441–449 [CrossRef]
     [Google Scholar]
  5. Blanpain C., Wittamer V., Vanderwinden J. M., Boom A., Renneboog B., Lee B., Le Poul E., El Asmar L., Govaerts C. other authors 2001; Palmitoylation of CCR5 is critical for receptor trafficking and efficient activation of intracellular signaling pathways. J Biol Chem 276:23795–23804 [CrossRef]
     [Google Scholar]
  6. Bodaghi B., Jones T. R., Zipeto D., Vita C., Sun L., Laurent L., Arenzana-Seisdedos F., Virelizier J. L., Michelson S. 1998; Chemokine sequestration by viral chemoreceptors as a novel viral escape strategy: withdrawal of chemokines from the environment of cytomegalovirus-infected cells. J Exp Med 188:855–866 [CrossRef]
     [Google Scholar]
  7. Buxton D., Reid H. W. 1980; Transmission of malignant catarrhal fever to rabbits. Vet Rec 106:243–245 [CrossRef]
     [Google Scholar]
  8. Cannon M., Philpott N. J., Cesarman E. 2003; The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor has broad signaling effects in primary effusion lymphoma cells. J Virol 77:57–67 [CrossRef]
     [Google Scholar]
  9. Coulter L. J., Wright H., Reid H. W. 2001; Molecular genomic characterization of the viruses of malignant catarrhal fever. J Comp Pathol 124:2–19 [CrossRef]
     [Google Scholar]
  10. Couty J. P., Gershengorn M. C. 2005; G-protein-coupled receptors encoded by human herpesviruses. Trends Pharmacol Sci 26:405–411 [CrossRef]
     [Google Scholar]
  11. Dewals B., Boudry C., Gillet L., Markine-Goriaynoff N., de Leval L., Haig D. M., Vanderplasschen A. 2006; Cloning of the genome of Alcelaphine herpesvirus 1 as an infectious and pathogenic bacterial artificial chromosome. J Gen Virol 87:509–517 [CrossRef]
     [Google Scholar]
  12. Ensser A., Pflanz R., Fleckenstein B. 1997; Primary structure of the alcelaphine herpesvirus 1 genome. J Virol 71:6517–6525
     [Google Scholar]
  13. Fraile-Ramos A., Kledal T. N., Pelchen-Matthews A., Bowers K., Schwartz T. W., Marsh M. 2001; The human cytomegalovirus US28 protein is located in endocytic vesicles and undergoes constitutive endocytosis and recycling. Mol Biol Cell 12:1737–1749 [CrossRef]
     [Google Scholar]
  14. Fraile-Ramos A., Pelchen-Matthews A., Kledal T. N., Browne H., Schwartz T. W., Marsh M. 2002; Localization of HCMV UL33 and US27 in endocytic compartments and viral membranes. Traffic 3:218–232 [CrossRef]
     [Google Scholar]
  15. Ghattas I. R., Sanes J. R., Majors J. E. 1991; The encephalomyocarditis virus internal ribosome entry site allows efficient coexpression of two genes from a recombinant provirus in cultured cells and in embryos. Mol Cell Biol 11:5848–5859
     [Google Scholar]
  16. Gillet L., Daix V., Donofrio G., Wagner M., Koszinowski U. H., China B., Ackermann M., Markine-Goriaynoff N., Vanderplasschen A. 2005; Development of bovine herpesvirus 4 as an expression vector using bacterial artificial chromosome cloning. J Gen Virol 86:907–917 [CrossRef]
     [Google Scholar]
  17. Holst P. J., Rosenkilde M. M. 2003; Microbiological exploitation of the chemokine system. Microbes Infect 5:179–187 [CrossRef]
     [Google Scholar]
  18. Huynh H. T., Robitaille G., Turner J. D. 1991; Establishment of bovine mammary epithelial cells (MAC-T): an in vitro model for bovine lactation. Exp Cell Res 197:191–199 [CrossRef]
     [Google Scholar]
  19. Le Poul E., Hisada S., Mizuguchi Y., Dupriez V. J., Burgeon E., Detheux M. 2002; Adaptation of aequorin functional assay to high throughput screening. J Biomol Screen 7:57–65 [CrossRef]
     [Google Scholar]
  20. Li H., Shen D. T., Knowles D. P., Gorham J. R., Crawford T. B. 1994; Competitive inhibition enzyme-linked immunosorbent assay for antibody in sheep and other ruminants to a conserved epitope of malignant catarrhal fever virus. J Clin Microbiol 32:1674–1679
     [Google Scholar]
  21. Marinissen M. J., Gutkind J. S. 2001; G-protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol Sci 22:368–376 [CrossRef]
     [Google Scholar]
  22. Markine-Goriaynoff N., Georgin J. P., Goltz M., Zimmermann W., Broll H., Wamwayi H. M., Pastoret P. P., Sharp P. M., Vanderplasschen A. 2003; The core 2 β -1,6- N -acetylglucosaminyltransferase-mucin encoded by bovine herpesvirus 4 was acquired from an ancestor of the African buffalo. J Virol 77:1784–1792 [CrossRef]
     [Google Scholar]
  23. Minamide L. S., Bamburg J. R. 1990; A filter paper dye-binding assay for quantitative determination of protein without interference from reducing agents or detergents. Anal Biochem 190:66–70 [CrossRef]
     [Google Scholar]
  24. O'Connor C. M., Kedes D. H. 2006; Mass spectrometric analyses of purified rhesus monkey rhadinovirus reveal 33 virion-associated proteins. J Virol 80:1574–1583 [CrossRef]
     [Google Scholar]
  25. Paulsen S. J., Rosenkilde M. M., Eugen-Olsen J., Kledal T. N. 2005; Epstein-Barr virus-encoded BILF1 is a constitutively active G protein-coupled receptor. J Virol 79:536–546 [CrossRef]
     [Google Scholar]
  26. Plowright W., Ferris R. D., Scott G. R. 1960; Blue wildebeest and the aetiological agent of bovine malignant fever. Nature 188:1167–1169 [CrossRef]
     [Google Scholar]
  27. Plowright W., Herniman K. A., Jessett D. M., Kalunda M., Rampton C. S. 1975; Immunisation of cattle against the herpesvirus of malignant catarrhal fever: failure of inactivated culture vaccines with adjuvant. Res Vet Sci 19:159–166
     [Google Scholar]
  28. Reid H. W. 2000; Malignant catarrhal fever. Infect Dis Rev 2:20–22
     [Google Scholar]
  29. Rosenkilde M. M. 2005; Virus-encoded chemokine receptors – putative novel antiviral drug targets. Neuropharmacology 48:1–13 [CrossRef]
     [Google Scholar]
  30. Rosenkilde M. M., Schwartz T. W. 2000; Potency of ligands correlates with affinity measured against agonist and inverse agonists but not against neutral ligand in constitutively active chemokine receptor. Mol Pharmacol 57:602–609
     [Google Scholar]
  31. Swa S., Wright H., Thomson J., Reid H., Haig D. 2001; Constitutive activation of Lck and Fyn tyrosine kinases in large granular lymphocytes infected with the gamma-herpesvirus agents of malignant catarrhal fever. Immunology 102:44–52 [CrossRef]
     [Google Scholar]
  32. Traul D. L., Elias S., Taus N. S., Herrmann L. M., Oaks J. L., Li H. 2005; A real-time PCR assay for measuring alcelaphine herpesvirus-1 DNA. J Virol Methods 129:186–190 [CrossRef]
     [Google Scholar]
  33. Vanderplasschen A., Markine-Goriaynoff N., Lomonte P., Suzuki M., Hiraoka N., Yeh J. C., Bureau F., Willems L., Thiry E. other authors 2000; A multipotential β -1,6- N -acetylglucosaminyl-transferase is encoded by bovine herpesvirus type 4. Proc Natl Acad Sci U S A 97:5756–5761 [CrossRef]
     [Google Scholar]
  34. Wright H., Stewart J. P., Ireri R. G., Campbell I., Pow I., Reid H. W., Haig D. M. 2003; Genome re-arrangements associated with loss of pathogenicity of the gamma-herpesvirus alcelaphine herpesvirus-1. Res Vet Sci 75:163–168 [CrossRef]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83153-0
Loading
The A5 gene of alcelaphine herpesvirus 1 encodes a constitutively active G-protein-coupled receptor that is non-essential for the induction of malignant catarrhal fever in rabbits
J. Gen. Virol. 88, 3224 (2007); https://doi.org/10.1099/vir.0.83153-0
/content/journal/jgv/10.1099/vir.0.83153-0
/content/journal/jgv/10.1099/vir.0.83153-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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