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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #193644
Title: Activation of microglia by Borna disease virus infection: in vitro study

Author
item OVANESOV, MIKHAIL - JOHNS HOPKINS UNIVERSITY
item SAUDER, CHRISTIAN - FOOD AND DRUG ADMIN
item RUBIN, STEVEN - JOHNS HOPKINS UNIVERSITY
item Richt, Juergen
item NATH, AVINDRA - JOHNS HOPKINS UNIVERSITY
item CARBONE, KATHRYN - FOOD AND DRUG ADMIN
item PLETNIKOV, MIKHAIL - JOHNS HOPKINS UNIVERSITY

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/15/2006
Publication Date: 12/1/2006
Citation: Ovanesov, M.V., Sauder, C., Rubin, S.A., Richt, J., Nath, A., Carbone, K.M., Pletnikov, M.V. 2006. Activation of microglia by Borna disease virus infection: in vitro study. Journal of Virology. 80(24):12141-12148.

Interpretive Summary: Borna disease virus (BDV) causes a persistent infection of the central nervous system associated with non-protective immune responses. Borna disease is actually caused by side effects of the immune response to the viral infection, not by the virus itself. BDV can infect a wide range of warm-blooded animals with horses and sheep being the main natural hosts; there is speculation that BDV can also infect humans. This work in a neonatal rat model of Borna disease, evaluates the mechanisms of microglia activation (microgliosis) observed in the brain of rats after BDV-infection. Direct exposure of primary microglia to BDV, BDV-infected neurons and astrocytes or apoptotic BDV-infected neurons did not activate microglia in vitro, suggesting that microgliosis in vivo might not directly result from BDV infection. This study contributes to our understanding of the role of these cells in viral infections of the brain.

Technical Abstract: 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 1-Beta, 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.