Biology and neurobiology of Borna disease viruses (BDV), defined by antibodies, neutralizability and their pathogenic potential

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Abstract
Borna disease viruses (BDV) isolated from more than 20 naturally infected horses, 2 sheep and a possible feline isolate were included in these studies. Most of these wild-type viruses were grown in rabbit cells. Specifically rabbit-adapted viruses establish persistent infection in immortalized cell lines of various animal species. Brain-, tissue culture-, and cell-free released viruses could all be neutralized with antibodies from naturally and experimentally infected animals (horse; hamster, rat, rabbit, mouse, and chicken), with highest titres in birds. Splenectomized rabbits, which were subsequently infected with BDV, efficiently produced high titres of neutralizing antibodies. All of the neutralizing sera and cerebrospinal fluids from infected animals inhibited tissue culture spread of BDV. Experimental infection and hyperimmunization induced antibodies directed against the major components of the soluble antigen (60, 40/38, 25 and 14.5 kD proteins). Analysis of the s-antigen complex with these sera and 6 stable monoclonal antibodies revealed that it consists of 40/38 and 25 kD proteins. Although each of these antibodies detected intracellular virus-specific structures they did not recognize outer plasmamembrane antigens, showed no cross-reactivity, and had no neutralizing capacity. Unifying pathogenetic concepts of this neurotropic virus and its structural elements are discussed.