Our preliminary experiments with Borna Virus infected rats showed that this animal pathogen, native to Eastern Europe, has highly unusual pathogenic mechanisms and may be a new type of animal virus. First, the virus apparently replicates only in neural tissues, where it causes persistent infection. This makes BV virus the only obligate neural pathogen known among animal viruses. Second, inoculation of adult rats results in an immune mediated but transient encephalitis which causes lysis of neurons in the limbic system and is accompanied by bizarre behavioral disease. Third, despite persistent virus replication in brain, the encephalitis remits and lysis of neurons ceases. Frenzied behavior changes to apathy. Thus, essentially, this is a new disease with a novel pathogenesis and provides a relevant model for studying mechanisms of chronic human neurological disease characterized also by loss of selected cell populations. We propose to purify Borna virus and characterize its physical, chemical and immunological properties so that the molecular properties of the virus can be correlated with its unique biological properties. Secondly, we will investigate the mechanism of persistence of the agent in the nervous system by tracing its route of dissemination, and identifying cell targets for replication, with emphasis on those cells attacked, and those spared, by the immunologically specific, cytolytic inflammatory response. Third, the mechanism of the short lived nature of the necrotizing encephalitis will be evaluated by assessing a hypothetical role for late developing suppressor cells supplanting acute cytolytic cell responses. Lymphocytes will be cultivated from infected animals during the aggressive and passive stages of disease, cultivated in vitro, and identified in functional tests and with monoclonal antibodies. The cells will be evaluated biologically in the animal in adoptive transfer experiments. Fourth, as a followup to recent reports, we will determine, primarily in immunocytochemical tests, whether a Borna-like virus is associated with certain forms of human neurological and neuropsychiatric disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023100-04
Application #
3406226
Study Section
Experimental Virology Study Section (EVR)
Project Start
1985-12-01
Project End
1989-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Lipkin, W I; Travis, G H; Carbone, K M et al. (1990) Isolation and characterization of Borna disease agent cDNA clones. Proc Natl Acad Sci U S A 87:4184-8
Carbone, K M; Trapp, B D; Griffin, J W et al. (1989) Astrocytes and Schwann cells are virus-host cells in the nervous system of rats with Borna disease. J Neuropathol Exp Neurol 48:631-44
Duchala, C S; Carbone, K M; Narayan, O (1989) Preliminary studies on the biology of Borna disease virus. J Gen Virol 70 ( Pt 12):3507-11