Volume 2 Supplement 1

Infectious diseases of the nervous system: pathogenesis and worldwide impact

Open Access

Borna disease virus phosphoprotein interferes with neuronal function and contributes to neurobehavioral disorders

  • Christine Prat1,
  • Sonja Schmid2,
  • Martin Schwemmle2 and
  • Daniel Gonzalez-Dunia1Email author
BMC Proceedings20082(Suppl 1):P56

https://doi.org/10.1186/1753-6561-2-s1-p56

Published: 23 September 2008

Infection by Borna disease virus (BDV) enables the study of the molecular mechanisms whereby a virus can persist in the central nervous system and lead to altered brain function, in the absence of overt cytolysis and inflammation. This neurotropic virus infects a wide variety of vertebrates and causes behavioral diseases. The basis of BDV-induced behavioral impairment remains largely unknown.

Previously, we have shown that BDV specifically blocks the activity-dependent enhancement of synaptic activity, both by studying the recycling of synaptic vesicles and by using electrophysiological approaches on BDV-infected neuronal networks grown on microelectrode arrays. This suggested defects in long-term potentiation, one key component of learning at the cellular level. Studies of signaling pathways involved in synaptic potentiation revealed that this blockade was due to an interference with PKC-dependent signaling in neurons, likely due to the viral phosphoprotein (P).

Here, we used recombinant BDV with mutated PKC phosphorylation sites on P [1], and showed that this mutation restored the phosphorylation of PKC substrates in neurons after stimulation. Moreover, using primary neuronal cultures grown on micro-electrode arrays (MEA), we provide evidence that the activity-dependent enhancement of synaptic activity was restored when cultures were infected with the P-mutated virus. Therefore, preventing P protein phosphorylation by PKC completely restores normal neuronal activity upon stimulation in infected neurons.

Together, these findings illustrate a novel mechanism whereby a viral protein can cause synaptic dysfunction and contribute to neurobehavioral disorders.

Authors’ Affiliations

(1)
INSERM U563
(2)
Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg

References

  1. Schmid S, Mayer D, Schneider U, Schwemmle M: Functional characterization of the major and minor phosphorylation sites of the P protein of Borna disease virus. J Virol. 2007, 81: 5497-5507. 10.1128/JVI.02233-06.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Prat et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

Advertisement