Borna disease virus induces acute fatal neurological disorders in neonatal gerbils without virus- and immune-mediated cell destructions.
Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that is known to cause neurological disturbances in various animal species. Our previous experiment demonstrated that neonate gerbils develop an acute fatal neurological disease following infection with BDV, Virology 282, 65-76). The study suggested that BDV directly causes functional damage of neuronal cells resulting in the lethal disorder in neonatal gerbils. To extend this finding, we examined whether BDV can induce neurological diseases in the absence of virus- and immune-mediated cell destruction, by using cyclosporine A (CsA)-treated neonatal gerbils. Although CsA completely suppressed specific antibody production and brain inflammation in the infected gerbil brains, the fatal neurological disorder was not inhibited by the treatment. Furthermore, we demonstrated that CsA treatment significantly decreased brain levels of cytokines, except interleukin (IL)-1 beta, in the infected gerbils. These results suggested that BDV replication, as well as brain cytokines, at least IL-1 beta, rapidly induces fatal disturbances in gerbil brain. We demonstrate here that BDV exhibits a unique neuropathogenesis in neonatal gerbil that may be pathologically and immunologically different from those in two other established rodent models, rats and mice. With this novel rodent model of virus infection it should be possible not only to examine acute neurological disturbances without severe neuroanatomical and immunopathological alterations but also to analyze molecular and cellular damage by virus replication in the central nervous system.
Watanabe
Makiko
M
Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Lee
Byeong-Jae
BJ
Yamashita
Makiko
M
Kamitani
Wataru
W
Kobayashi
Takeshi
T
Tomonaga
Keizo
K
Ikuta
Kazuyoshi
K
D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D001890:Borna Disease / Q000276:immunology / Q000473:pathology / Q000821:virology*; D001891:Borna disease virus / Q000302:isolation & purification / Q000472:pathogenicity*; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002493:Central Nervous System Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology*; D016572:Cyclosporine / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005849:Gerbillinae / Q000821:virology; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007375:Interleukin-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D014774:Virulence; D014779:Virus Replication
D016207:Cytokines; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D012333:RNA, Messenger; D016572:Cyclosporine