Advertisement

Archives of Virology

, Volume 155, Issue 5, pp 789–793 | Cite as

Protein kinase C-dependent phosphorylation of Borna disease virus P protein is required for efficient viral spread

  • Sonja Schmid
  • Philippe Metz
  • Christine M. A. Prat
  • Daniel Gonzalez-Dunia
  • Martin Schwemmle
Brief Report

Abstract

Mutational analysis of the phosphate acceptor sites of the Borna disease virus (BDV) phosphoprotein (P) has suggested a role of phosphorylation for viral spread. However, the studied mutant viruses also had two amino acid exchanges in the X protein, because the reading frames of P and X overlap. To determine the relative contribution of P and X to viral attenuation, we studied a P variant with serine-to-leucine substitutions (PS26L,S28L) in which the wild-type X sequence was conserved. Viral spread of rBDV-PS26L,S28L was impaired in human oligodendroglioma cells and in adult rats. Thus, BDV-P phosphorylation contributes to efficient viral dissemination.

Keywords

Rabies Vero Cell Polymerase Activity Viral Life Cycle Human Respiratory Syncytial Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft. We thank members of the Schwemmle and Gonzalez-Dunia labs for critical reading of the manuscript.

References

  1. 1.
    Gonzalez-Dunia D, Volmer R, Mayer D, Schwemmle M (2005) Borna disease virus interference with neuronal plasticity. Virus Res 111(2):224–234CrossRefPubMedGoogle Scholar
  2. 2.
    Briese T, De la Torre JC, Lewis A, Ludwig H, Lipkin WI (1992) Borna disease virus, a negative-strand RNA virus, transcribes in the nucleus of infected cells. Proc Natl Acad Sci USA 89:11486–11489CrossRefPubMedGoogle Scholar
  3. 3.
    Schneider PA, Schneemann A, Lipkin WI (1994) RNA splicing in Borna disease virus, a nonsegmented, negative-strand RNA virus. J Virol 68(8):5007–5012PubMedGoogle Scholar
  4. 4.
    Schneider U, Martin A, Schwemmle M, Staeheli P (2007) Genome trimming by Borna disease viruses: viral replication control or escape from cellular surveillance? Cell Mol Life Sci 64(9):1038–1042CrossRefPubMedGoogle Scholar
  5. 5.
    Schwemmle M, Salvatore M, Shi L, Richt J, Lee CH, Lipkin WI (1998) Interactions of the borna disease virus P, N, and X proteins and their functional implications. J Biol Chem 273(15):9007–9012CrossRefPubMedGoogle Scholar
  6. 6.
    Schneider U, Blechschmidt K, Schwemmle M, Staeheli P (2004) Overlap of interaction domains indicates a central role of the P protein in assembly and regulation of the Borna disease virus polymerase complex. J Biol Chem 279(53):55290–55296CrossRefPubMedGoogle Scholar
  7. 7.
    Schwemmle M, De B, Shi L, Banerjee A, Lipkin WI (1997) Borna disease virus P-protein is phosphorylated by protein kinase Cepsilon and casein kinase II. J Biol Chem 272(35):21818–21823CrossRefPubMedGoogle Scholar
  8. 8.
    Pattnaik AK, Hwang L, Li T, Englund N, Mathur M, Das T, Banerjee AK (1997) Phosphorylation within the amino-terminal acidic domain I of the phosphoprotein of vesicular stomatitis virus is required for transcription but not for replication. J Virol 71(11):8167–8175PubMedGoogle Scholar
  9. 9.
    Das SC, Pattnaik AK (2004) Phosphorylation of vesicular stomatitis virus phosphoprotein P is indispensable for virus growth. J Virol 78(12):6420–6430CrossRefPubMedGoogle Scholar
  10. 10.
    Hwang LN, Englund N, Das T, Banerjee AK, Pattnaik AK (1999) Optimal replication activity of vesicular stomatitis virus RNA polymerase requires phosphorylation of a residue(s) at carboxy-terminal domain II of its accessory subunit, phosphoprotein P. J Virol 73(7):5613–5620PubMedGoogle Scholar
  11. 11.
    Schmid S, Mayer D, Schneider U, Schwemmle M (2007) Functional characterization of the major and minor phosphorylation sites of the P protein of Borna disease virus. J Virol 81(11):5497–5507CrossRefPubMedGoogle Scholar
  12. 12.
    Schneider U, Naegele M, Staeheli P, Schwemmle M (2003) Active borna disease virus polymerase complex requires a distinct nucleoprotein-to-phosphoprotein ratio but no viral X protein. J Virol 77(21):11781–11789CrossRefPubMedGoogle Scholar
  13. 13.
    Poenisch M, Burger N, Staeheli P, Bauer G, Schneider U (2009) Protein X of borna disease virus inhibits apoptosis and promotes viral persistence in the central nervous systems of newborn-infected rats. J Virol 83(9):4297–4307CrossRefPubMedGoogle Scholar
  14. 14.
    Poenisch M, Wille S, Ackermann A, Staeheli P, Schneider U (2007) The X protein of borna disease virus serves essential functions in the viral multiplication cycle. J Virol 81(13):7297–7299CrossRefPubMedGoogle Scholar
  15. 15.
    Buchholz UJ, Finke S, Conzelmann KK (1999) Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter. J Virol 73(1):251–259PubMedGoogle Scholar
  16. 16.
    Ribeiro EA Jr, Favier A, Gerard FC, Leyrat C, Brutscher B, Blondel D, Ruigrok RW, Blackledge M, Jamin M (2008) Solution structure of the C-terminal nucleoprotein-RNA binding domain of the vesicular stomatitis virus phosphoprotein. J Mol Biol 382(2):525–538CrossRefPubMedGoogle Scholar
  17. 17.
    Longhi S (2009) Nucleocapsid structure and function. Curr Top Microbiol Immunol 329:103–128CrossRefPubMedGoogle Scholar
  18. 18.
    Schneider U (2005) Novel insights into the regulation of the viral polymerase complex of neurotropic Borna disease virus. Virus Res 111(2):148–160CrossRefPubMedGoogle Scholar
  19. 19.
    Prat CM, Schmid S, Farrugia F, Cenac N, Le Masson G, Schwemmle M, Gonzalez-Dunia D (2009) Mutation of the protein kinase C site in borna disease virus phosphoprotein abrogates viral interference with neuronal signaling and restores normal synaptic activity. PLoS Pathog 5(5):e1000425CrossRefPubMedGoogle Scholar
  20. 20.
    Hallensleben W, Staeheli P (1999) Inhibition of Borna disease virus multiplication by interferon: cell line differences in susceptibility. Arch Virol 144(6):1209–1216CrossRefPubMedGoogle Scholar
  21. 21.
    Jacob Y, Badrane H, Ceccaldi PE, Tordo N (2000) Cytoplasmic dynein LC8 interacts with lyssavirus phosphoprotein. J Virol 74(21):10217–10222CrossRefPubMedGoogle Scholar
  22. 22.
    Raux H, Flamand A, Blondel D (2000) Interaction of the rabies virus P protein with the LC8 dynein light chain. J Virol 74(21):10212–10216CrossRefPubMedGoogle Scholar
  23. 23.
    Asenjo A, Rodriguez L, Villanueva N (2005) Determination of phosphorylated residues from human respiratory syncytial virus P protein that are dynamically dephosphorylated by cellular phosphatases: a possible role for serine 54. J Gen Virol 86(Pt 4):1109–1120CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Sonja Schmid
    • 1
    • 3
  • Philippe Metz
    • 1
    • 4
  • Christine M. A. Prat
    • 2
  • Daniel Gonzalez-Dunia
    • 2
  • Martin Schwemmle
    • 1
  1. 1.Department of Virology, Institute for Medical Microbiology and HygieneUniversity of FreiburgFreiburgGermany
  2. 2.INSERM U563, Centre de Physiopathologie de Toulouse PurpanUniversité Paul-SabatierToulouseFrance
  3. 3.Department of MicrobiologyMount Sinai School of MedicineNew YorkUSA
  4. 4.Department of Molecular VirologyUniversity of HeidelbergHeidelbergGermany

Personalised recommendations