CLINICAL SIMILARITIES AND CLOSE GENETIC-RELATIONSHIP OF HUMAN AND ANIMAL BORNA-DISEASE-VIRUS

Borna disease virus (BDV) is the prototype genus of a new family, Born aviridne, within the order Mononegavirales. BDV naturally infects anim als and man. The symptomatology in animals ranges from subclinical inf ection to rare cases of encephalitis. Asymptomatic infection seemed mo re frequent than expected, based on antibody data from 100 healthy hor ses derived from different stables with a history of diseased cases (3 0-40% carriers). Likewise, phasic episodes of a neurobehavioral syndro me followed by recovery were much more common than fatal neurologic di sease. They were paralleled by expression of BDV antigens (N-protein p 40, P-protein p24) and RNA transcripts in peripheral blood mononuclear cells, indicating viral activation. Representative longitudinal studi es showed that episodes of depressive illness in humans as well as apa thetic phases in infected horses were accompanied by antigen expressio n and followed a similar clinical course. After recovery, BDV antigen disappeared. This temporal congruence, together with the recent isolat ion of infectious BDV from such patients, points to a contributory rol e of this virus in human affective disorders. Successful amelioration of BDV-induced neurobehavioral disease in horses with antidepressants applied in psychiatry, supported a common viral pathomechanism, involv ing reversible disturbances of the neurotransmitter network in the lim bic system. Sequences of genetic material amplified from infected anim al tissue and human PBMCs revealed a close interspecies relationship a nd high sequence conservation of the BDV genome. In human BDV isolates , however, single unique mutations were prominent in four genes. This finding supports the hypothesis that despite of high genomic conservat ion, species-specific genotypes may be definable, provided the sequenc es are derived from RNA of infectious virus.