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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #182709
Title: EXPRESSION OF ALLOGRAFT INFLAMMATORY FACTOR-1 AND HAEME OXYGENASE-1 IN BRAINS OF RATS INFECTED WITH THE NEUROTROPIC BORNA DISEASE VIRUS

Author
item HERDEN, C - HANNOVER, GERMANY
item SCHLUESENER, H - TUBINGEN, GERMANY
item Richt, Juergen

Submitted to: Neuropathology and Applied Neurobiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/28/2005
Publication Date: 10/1/2005
Citation: Herden, C., Schluesener, H.J., Richt, J.A. 2005. Expression of allograft inflammatory factor-1 and haeme oxygenase-1 in brains of rats infected with the neurotropic Borna disease virus. Neuropathology and Applied Neurobiology. 31(5):512-21.

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 rat model of Borna disease, identified activation of certain types of brain cells as a contributor to development of clinical disease. This study contributes to our understanding of the role of these cells in viral infections of the brain.

Technical Abstract: Experimental infection of Lewis rats with Borna disease virus (BDV) causes an immune-mediated nonpurulent meningoencephalitis. Viral persistence in the CNS is accompanied by mononuclear infiltrates, activated monocytic/microglial cells and reactive astrocytes. The immune-mediated process was further characterised by expression analysis of allograft inflammatory factor-1 (AIF-1), a novel marker of monocyte/microglial activation and of glial fibrillary acid protein (GFAP) between day 3 and 50 post infection (p.i.). Potential neuroprotective effects of these cells were studied by the induction of haeme oxygenase-1 (HO-1), a defensive molecule against oxidative stress in various brain insults. In BDV-infected rat brains, mononuclear infiltrates and AIF-1 expression increased up to day 28 p.i. Early p.i., AIF-1 expression was mainly found in inflammatory lesions and adjacent brain parenchyma. Already 24 days p.i., a widespread up regulation of AIF-1 was observed which declined only moderately beyond day 28 p.i. HO-1 induction was maximal between days 18 and 28 p.i. Increased amounts of GFAP-positive astrocytes were present beyond 24 days p.i. Viral antigen expression increased simultaneously to the inflammatory reaction and persisted up to 50 days p.i. Widespread up regulation of AIF-1 indicates an early, long lasting microglial activation which might be involved in the immune surveillance of the immune-mediated inflammatory events. The early peak of HO-1 most likely represents a neuroprotective, anti-inflammatory response by invading monocytes, microglial cells and astrocytes during the formation of encephalitic lesions and acute viral replication.