Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1997 Apr;71(4):3208–3218. doi: 10.1128/jvi.71.4.3208-3218.1997

Characterization of Borna disease virus p56 protein, a surface glycoprotein involved in virus entry.

D Gonzalez-Dunia 1, B Cubitt 1, F A Grasser 1, J C de la Torre 1
PMCID: PMC191453  PMID: 9060684

Abstract

Borna disease virus (BDV) is a nonsegmented negative-stranded (NNS) RNA virus, prototype of a new taxon in the Mononegavirales order. BDV causes neurologic disease manifested by behavioral abnormalities in several animal species, and evidence suggests that it may be a human pathogen. To improve our knowledge about the biology of this novel virus, we have identified and characterized the product of BDV open reading frame IV (BVp56). Based on sequence features, BVp56 encodes a virus surface glycoprotein. Glycoproteins play essential roles in the biology of NNS RNA viruses. Expression of BVp56 resulted in the generation of two polypeptides with molecular masses of about 84 and 43 kDa (GP-84 and GP-43). GP-84 and GP-43 likely correspond to the full-length BVp56 gene and to its C terminus, respectively. Endoglycosidase studies demonstrated that both products were glycosylated and that this process was required for the stabilization of newly synthesized products. Moreover, our results suggested that GP-43 is generated by cleavage of GP-84 by a cellular protease. Subcellular localization studies demonstrated that GP-84 accumulates in the ER, whereas GP-43 reaches the cell surface. Both BVp56 products were found to be associated with infectious virions, and antibodies to BVp56 had neutralizing activity. Our findings suggest that BVp56 exhibits a novel form of processing for an animal NNS RNA virus surface glycoprotein, which might influence the assembly and budding of BDV.

Full Text

The Full Text of this article is available as a PDF (876.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bode L. Human infections with Borna disease virus and potential pathogenic implications. Curr Top Microbiol Immunol. 1995;190:103–130. doi: 10.1007/978-3-642-78618-1_7. [DOI] [PubMed] [Google Scholar]
  2. Briese T., Schneemann A., Lewis A. J., Park Y. S., Kim S., Ludwig H., Lipkin W. I. Genomic organization of Borna disease virus. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4362–4366. doi: 10.1073/pnas.91.10.4362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Briese T., de la Torre J. C., Lewis A., Ludwig H., Lipkin W. I. Borna disease virus, a negative-strand RNA virus, transcribes in the nucleus of infected cells. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11486–11489. doi: 10.1073/pnas.89.23.11486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carbone K. M., Rubin S. A., Sierra-Honigmann A. M., Lederman H. M. Characterization of a glial cell line persistently infected with borna disease virus (BDV): influence of neurotrophic factors on BDV protein and RNA expression. J Virol. 1993 Mar;67(3):1453–1460. doi: 10.1128/jvi.67.3.1453-1460.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chakrabarti S., Brechling K., Moss B. Vaccinia virus expression vector: coexpression of beta-galactosidase provides visual screening of recombinant virus plaques. Mol Cell Biol. 1985 Dec;5(12):3403–3409. doi: 10.1128/mcb.5.12.3403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chatterjee S., Sarkar S. Studies on endoplasmic reticulum--Golgi complex cycling pathway in herpes simplex virus-infected and brefeldin A-treated human fibroblast cells. Virology. 1992 Nov;191(1):327–337. doi: 10.1016/0042-6822(92)90195-u. [DOI] [PubMed] [Google Scholar]
  7. Compans R. W., Melsen L. R., de la Torre J. C. Virus-like particles in MDCK cells persistently infected with Borna disease virus. Virus Res. 1994 Sep;33(3):261–268. doi: 10.1016/0168-1702(94)90107-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cubitt B., Oldstone C., Valcarcel J., Carlos de la Torre J. RNA splicing contributes to the generation of mature mRNAs of Borna disease virus, a non-segmented negative strand RNA virus. Virus Res. 1994 Oct;34(1):69–79. doi: 10.1016/0168-1702(94)90120-1. [DOI] [PubMed] [Google Scholar]
  9. Cubitt B., Oldstone C., de la Torre J. C. Sequence and genome organization of Borna disease virus. J Virol. 1994 Mar;68(3):1382–1396. doi: 10.1128/jvi.68.3.1382-1396.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cubitt B., de la Torre J. C. Borna disease virus (BDV), a nonsegmented RNA virus, replicates in the nuclei of infected cells where infectious BDV ribonucleoproteins are present. J Virol. 1994 Mar;68(3):1371–1381. doi: 10.1128/jvi.68.3.1371-1381.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. De La Torre J. C., Gonzalez-Dunia D., Cubitt B., Mallory M., Mueller-Lantzsch N., Grässer F. A., Hansen L. A., Masliah E. Detection of borna disease virus antigen and RNA in human autopsy brain samples from neuropsychiatric patients. Virology. 1996 Sep 15;223(2):272–282. doi: 10.1006/viro.1996.0479. [DOI] [PubMed] [Google Scholar]
  12. Fuerst T. R., Niles E. G., Studier F. W., Moss B. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122–8126. doi: 10.1073/pnas.83.21.8122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Garten W., Hallenberger S., Ortmann D., Schäfer W., Vey M., Angliker H., Shaw E., Klenk H. D. Processing of viral glycoproteins by the subtilisin-like endoprotease furin and its inhibition by specific peptidylchloroalkylketones. Biochimie. 1994;76(3-4):217–225. doi: 10.1016/0300-9084(94)90149-x. [DOI] [PubMed] [Google Scholar]
  14. Gonzalez-Dunia D., Eddleston M., Mackman N., Carbone K., de la Torre J. C. Expression of tissue factor is increased in astrocytes within the central nervous system during persistent infection with borna disease virus. J Virol. 1996 Sep;70(9):5812–5820. doi: 10.1128/jvi.70.9.5812-5820.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gosztonyi G., Dietzschold B., Kao M., Rupprecht C. E., Ludwig H., Koprowski H. Rabies and borna disease. A comparative pathogenetic study of two neurovirulent agents. Lab Invest. 1993 Mar;68(3):285–295. [PubMed] [Google Scholar]
  16. Gosztonyi G., Ludwig H. Borna disease--neuropathology and pathogenesis. Curr Top Microbiol Immunol. 1995;190:39–73. [PubMed] [Google Scholar]
  17. Gregory D. W., Pirie B. J. Wetting agents for biological electron microscopy. I. General considerations and negative staining. J Microsc. 1973 Dec;99(3):251–255. doi: 10.1111/j.1365-2818.1973.tb04625.x. [DOI] [PubMed] [Google Scholar]
  18. Hallenberger S., Bosch V., Angliker H., Shaw E., Klenk H. D., Garten W. Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature. 1992 Nov 26;360(6402):358–361. doi: 10.1038/360358a0. [DOI] [PubMed] [Google Scholar]
  19. Hobman T. C., Woodward L., Farquhar M. G. The rubella virus E2 and E1 spike glycoproteins are targeted to the Golgi complex. J Cell Biol. 1993 Apr;121(2):269–281. doi: 10.1083/jcb.121.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kishi M., Arimura Y., Ikuta K., Shoya Y., Lai P. K., Kakinuma M. Sequence variability of Borna disease virus open reading frame II found in human peripheral blood mononuclear cells. J Virol. 1996 Jan;70(1):635–640. doi: 10.1128/jvi.70.1.635-640.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Koerner T. J., Hill J. E., Myers A. M., Tzagoloff A. High-expression vectors with multiple cloning sites for construction of trpE fusion genes: pATH vectors. Methods Enzymol. 1991;194:477–490. doi: 10.1016/0076-6879(91)94036-c. [DOI] [PubMed] [Google Scholar]
  22. Ludwig H., Bode L., Gosztonyi G. Borna disease: a persistent virus infection of the central nervous system. Prog Med Virol. 1988;35:107–151. [PubMed] [Google Scholar]
  23. Niemann H., Geyer R., Klenk H. D., Linder D., Stirm S., Wirth M. The carbohydrates of mouse hepatitis virus (MHV) A59: structures of the O-glycosidically linked oligosaccharides of glycoprotein E1. EMBO J. 1984 Mar;3(3):665–670. doi: 10.1002/j.1460-2075.1984.tb01864.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pettersson R. F. Protein localization and virus assembly at intracellular membranes. Curr Top Microbiol Immunol. 1991;170:67–106. doi: 10.1007/978-3-642-76389-2_3. [DOI] [PubMed] [Google Scholar]
  25. Rott R., Becht H. Natural and experimental Borna disease in animals. Curr Top Microbiol Immunol. 1995;190:17–30. doi: 10.1007/978-3-642-78618-1_2. [DOI] [PubMed] [Google Scholar]
  26. Ruusala A., Persson R., Schmaljohn C. S., Pettersson R. F. Coexpression of the membrane glycoproteins G1 and G2 of Hantaan virus is required for targeting to the Golgi complex. Virology. 1992 Jan;186(1):53–64. doi: 10.1016/0042-6822(92)90060-3. [DOI] [PubMed] [Google Scholar]
  27. Sanchez A., Trappier S. G., Mahy B. W., Peters C. J., Nichol S. T. The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3602–3607. doi: 10.1073/pnas.93.8.3602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sauder C., Müller A., Cubitt B., Mayer J., Steinmetz J., Trabert W., Ziegler B., Wanke K., Mueller-Lantzsch N., de la Torre J. C. Detection of Borna disease virus (BDV) antibodies and BDV RNA in psychiatric patients: evidence for high sequence conservation of human blood-derived BDV RNA. J Virol. 1996 Nov;70(11):7713–7724. doi: 10.1128/jvi.70.11.7713-7724.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schlesinger M. J., Schlesinger S. Domains of virus glycoproteins. Adv Virus Res. 1987;33:1–44. doi: 10.1016/S0065-3527(08)60315-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schneemann A., Schneider P. A., Lamb R. A., Lipkin W. I. The remarkable coding strategy of borna disease virus: a new member of the nonsegmented negative strand RNA viruses. Virology. 1995 Jun 20;210(1):1–8. doi: 10.1006/viro.1995.1311. [DOI] [PubMed] [Google Scholar]
  31. Schneider P. A., Schneemann A., Lipkin W. I. RNA splicing in Borna disease virus, a nonsegmented, negative-strand RNA virus. J Virol. 1994 Aug;68(8):5007–5012. doi: 10.1128/jvi.68.8.5007-5012.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Spies C. P., Compans R. W. Alternate pathways of secretion of simian immunodeficiency virus envelope glycoproteins. J Virol. 1993 Nov;67(11):6535–6541. doi: 10.1128/jvi.67.11.6535-6541.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Squinto S. P., Aldrich T. H., Lindsay R. M., Morrissey D. M., Panayotatos N., Bianco S. M., Furth M. E., Yancopoulos G. D. Identification of functional receptors for ciliary neurotrophic factor on neuronal cell lines and primary neurons. Neuron. 1990 Dec;5(6):757–766. doi: 10.1016/0896-6273(90)90334-c. [DOI] [PubMed] [Google Scholar]
  34. Stieneke-Gröber A., Vey M., Angliker H., Shaw E., Thomas G., Roberts C., Klenk H. D., Garten W. Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease. EMBO J. 1992 Jul;11(7):2407–2414. doi: 10.1002/j.1460-2075.1992.tb05305.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Walker P. J., Byrne K. A., Riding G. A., Cowley J. A., Wang Y., McWilliam S. The genome of bovine ephemeral fever rhabdovirus contains two related glycoprotein genes. Virology. 1992 Nov;191(1):49–61. doi: 10.1016/0042-6822(92)90165-l. [DOI] [PubMed] [Google Scholar]
  36. Waltrip R. W., 2nd, Buchanan R. W., Summerfelt A., Breier A., Carpenter W. T., Jr, Bryant N. L., Rubin S. A., Carbone K. M. Borna disease virus and schizophrenia. Psychiatry Res. 1995 Jan 31;56(1):33–44. doi: 10.1016/0165-1781(94)02600-n. [DOI] [PubMed] [Google Scholar]
  37. Warren G. Protein transport. Signals and salvage sequences. Nature. 1987 May 7;327(6117):17–18. doi: 10.1038/327017a0. [DOI] [PubMed] [Google Scholar]
  38. Watanabe M., Hirano A., Stenglein S., Nelson J., Thomas G., Wong T. C. Engineered serine protease inhibitor prevents furin-catalyzed activation of the fusion glycoprotein and production of infectious measles virus. J Virol. 1995 May;69(5):3206–3210. doi: 10.1128/jvi.69.5.3206-3210.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. White S., Miller K., Hopkins C., Trowbridge I. S. Monoclonal antibodies against defined epitopes of the human transferrin receptor cytoplasmic tail. Biochim Biophys Acta. 1992 Jul 22;1136(1):28–34. doi: 10.1016/0167-4889(92)90081-l. [DOI] [PubMed] [Google Scholar]
  40. Whitton J. L., Southern P. J., Oldstone M. B. Analyses of the cytotoxic T lymphocyte responses to glycoprotein and nucleoprotein components of lymphocytic choriomeningitis virus. Virology. 1988 Feb;162(2):321–327. doi: 10.1016/0042-6822(88)90471-0. [DOI] [PubMed] [Google Scholar]
  41. Wickner W. T., Lodish H. F. Multiple mechanisms of protein insertion into and across membranes. Science. 1985 Oct 25;230(4724):400–407. doi: 10.1126/science.4048938. [DOI] [PubMed] [Google Scholar]
  42. Wright K. E., Salvato M. S., Buchmeier M. J. Neutralizing epitopes of lymphocytic choriomeningitis virus are conformational and require both glycosylation and disulfide bonds for expression. Virology. 1989 Aug;171(2):417–426. doi: 10.1016/0042-6822(89)90610-7. [DOI] [PubMed] [Google Scholar]
  43. Zimmermann W., Breter H., Rudolph M., Ludwig H. Borna disease virus: immunoelectron microscopic characterization of cell-free virus and further information about the genome. J Virol. 1994 Oct;68(10):6755–6758. doi: 10.1128/jvi.68.10.6755-6758.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. de la Torre J. C. Molecular biology of borna disease virus: prototype of a new group of animal viruses. J Virol. 1994 Dec;68(12):7669–7675. doi: 10.1128/jvi.68.12.7669-7675.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES