Expression of allograft inflammatory factor-1 and haeme oxygenase-1 in brains of rats infected with the neurotropic Borna disease virus.
Experimental infection of Lewis rats with Borna disease virus (BDV) causes an immune-mediated nonpurulent meningoencephalitis. Viral persistence in the central nervous system is accompanied by mononuclear infiltrates, activated monocytic/microglial cells and reactive astrocytes. The immune-mediated process was further characterized 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 day 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. During early time points p.i., AIF-1 expression was mainly found in inflammatory lesions and adjacent brain parenchyma. Already 24 days p.i., a widespread upregulation 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 upregulation of AIF-1 indicates an early, long-lasting microglial activation, which might be involved in the immunesurveillance 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.
Herden
C
C
Institut für Pathologie, Tierärztliche Hochschule Hannover, Bünteweg 17, D-30559 Hannover, Germany. Christiane.Herden@tiho-hannover.de
Schluesener
H J
HJ
Richt
J A
JA
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001253:Astrocytes / Q000378:metabolism / Q000821:virology; D001890:Borna Disease / Q000378:metabolism* / Q000473:pathology; D001891:Borna disease virus / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000502:physiology; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism / Q000821:virology; D051381:Rats; D011917:Rats, Inbred Lew
C100745:Aif1 protein, rat; D000956:Antigens, Viral; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1