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Journal of Virology, December 2006, p. 12141-12148, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01648-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Activation of Microglia by Borna Disease Virus Infection: In Vitro Study{triangledown}

Mikhail V. Ovanesov,1,2 Christian Sauder,2 Steven A. Rubin,2 Jürgen Richt,3 Avindra Nath,4 Kathryn M. Carbone,2 and Mikhail V. Pletnikov1,2*

Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland,1 CBER, U.S. Food and Drug Administration, Bethesda, Maryland,2 National Animal Disease Center, Ames, Iowa,3 Departments of Neurology and Neuroscience, Johns Hopkins University, Baltimore, Maryland4

Received 1 August 2006/ Accepted 15 September 2006

Neonatal Borna disease virus (BDV) infection of the rat brain is associated with microglial activation and damage to the certain neuronal populations. Since persistent BDV infection of neurons in vitro is noncytolytic and noncytopathic, activated microglia have been suggested to be responsible for neuronal cell death in vivo. However, the mechanisms of activation of microglia in neonatally BDV-infected rat brain have not been investigated. To address these issues, activation of primary rat microglial cells was studied following exposure to purified BDV or to persistently BDV-infected primary cortical neurons or after BDV infection of primary mixed neuron-glial cultures. Neither purified virus nor BDV-infected neurons alone activated primary microglia as assessed by the changes in cell shape or production of the proinflammatory cytokines. In contrast, in the BDV-infected primary mixed cultures, we observed proliferation of microglia cells that acquired the round morphology and expressed major histocompatibility complex molecules of classes I and II. These manifestations of microglia activation were observed in the absence of direct BDV infection of microglia or overt neuronal toxicity. In addition, compared to uninfected mixed cultures, activation of microglia in BDV-infected mixed cultures was associated with a significantly greater lipopolysaccharide-induced release of tumor necrosis factor alpha, interleukin 1ß, and interleukin 10. Taken together, the present data are the first in vitro evidence that persistent BDV infection of neurons and astrocytes rather than direct exposure to the virus or dying neurons is critical for activating microglia.

* Corresponding author. Mailing address: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, CMSC 8-121, Baltimore, MD 21287. Phone: (410) 502-3760. Fax: (410) 614-0013. E-mail: mpletnik{at}jhmi.edu.

{triangledown} Published ahead of print on 4 October 2006.

Journal of Virology, December 2006, p. 12141-12148, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01648-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ohtaki, N., Kamitani, W., Watanabe, Y., Hayashi, Y., Yanai, H., Ikuta, K., Tomonaga, K. (2007). Downregulation of an Astrocyte-Derived Inflammatory Protein, S100B, Reduces Vascular Inflammatory Responses in Brains Persistently Infected with Borna Disease Virus. J. Virol. 81: 5940-5948 [Abstract] [Full Text]  


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