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Journal of Virology, April 2000, p. 3441-3448, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Synaptic Pathology in Borna Disease Virus Persistent Infection

Daniel Gonzalez-Dunia,1,* Michiko Watanabe,2,dagger Sylvie Syan,1 Margaret Mallory,3 Eliezer Masliah,3 and Juan Carlos de la Torre2,*

Unité des Virus Lents, CNRS URA 1930, Institut Pasteur, Paris, France,1 and Department of Neuropharmacology, Division of Virology, The Scripps Research Institute,2 and Department of Neurosciences, University of California, San Diego,3 La Jolla, California

Received 27 September 1999/Accepted 18 January 2000

Borna disease virus (BDV) infection of newborn rats leads to a persistent infection of the brain, which is associated with behavioral and neuroanatonomical abnormalities. These disorders occur in the absence of lymphoid cell infiltrates, and BDV-induced cell damage is restricted to defined brain areas. To investigate if damage to synaptic structures anteceded neuronal loss in BDV neonatally infected rats, we analyzed at different times postinfection the expression levels of growth-associated protein 43 and synaptophysin, two molecules involved in neuroplasticity processes. We found that BDV induced a progressive and marked decrease in the expression of these synaptic markers, which was followed by a significant loss of cortical neurons. Our findings suggest that BDV persistent infection interferes with neuroplasticity processes in specific cell populations. This, in turn, could affect the proper supply of growth factors and other molecules required for survival of selective neuronal populations within the cortex and limbic system structures.

* Corresponding author. Mailing address for Daniel Gonzalez Dunia: Unité des Virus Lents, Institut Pasteur, 28, rue du Dr Roux, 75724 Paris Cedex 15, France. Phone: 33 1 45 68 87 71. Fax: 33 1 40 61 31 67. E-mail: ddune{at}pasteur.fr. Mailing address for Juan Carlos de la Torre: The Scripps Research Institute, IMM6, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-9462. Fax: (858) 784-9981. E-mail: juanct{at}scripps.edu.

dagger Present address: Department of Neurovirology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

Journal of Virology, April 2000, p. 3441-3448, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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