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, Bornaviridae, within the order Mononegavirales. BDV naturally infects animals and man. The symptomatology in animals ranges from subclinical infection to rare cases of encephalitis. Asympto
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Department of Virology, Robert Koch-Institut, Berlin, Federal Republic of Germany 2 Institute of Virology, Free University of Berlin, Berlin, Federal Republic of Germany
Summary. Borna disease virus (BDV) is the prototype genus of a new family, Bornaviridae, within the order Mononegavirales. BDV naturally infects animals and man. The symptomatology in animals ranges from subclinical infection to rare cases of encephalitis. Asymptomatic infection seemed more frequent than expected, based on antibody data from 100 healthy horses derived from different stables with a history of diseased cases (30-40% carriers). Likewise, phasic episodes of a neurobehavioral syndrome followed by recovery were much more common than fatal neurologic disease. They were paralleled by expression of BDV antigens (N-protein p40, P-protein p24) and RNA transcripts in peripheral blood mononuclear cells, indicating viral activation. Representative longitudinal studies showed that episodes of depressive illness in humans as well as apathetic phases in infected horses were accompanied by antigen expression and followed a similar clinical course. After recovery, BDV antigen disappeared. This temporal congruence, together with the recent isolation of infectious BDV from such patients, points to a contributory role of this virus in human affective disorders. Successful amelioration of BDVinduced neurobehavioral disease in horses with antidepressants applied in psychiatry, supported a common viral pathomechanism, involving reversible disturbances of the neurotransmitter network in the limbic system. Sequences of genetic material amplified from infected animal tissue and human PBMCs revealed a close interspecies relationship and 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 conservation, species-specific genotypes may be definable, provided the sequences are derived from RNA of infectious virus. Introduction
Borna disease virus (BDV) is an enveloped, nonsegmented, negative- and single-stranded (NNS) RNA virus within the order Mononegavirales [10,12,31].
O.-R. Kaaden et al. (eds.), Viral Zoonoses and Food of Animal Origin © Springer-Verlag/Wien 1997
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L. Bode and H. Ludwig
Analogously, its genome consists of five genes. Open reading frame (ORF) I (1110 nucleotides [nt]) encodes the N-protein (p40), ORF II (603 nt) the Pprotein (p24), ORF III (426 nt) the M-proteine (gp 16), ORF IV (1509 nt) the putative G-protein (gp 56), and ORF V (5145 nt) the L-polymerase of BDY. Based on similarities of the L-polymerase, BDV has a relatively close relationship to rabiesvirus. However, in contrast to all other animal NNS viruses, Bomavirus replicates in the nucleus of the infected cell [9, 11], a unique property, which led to its classification as the prototype of a new family (Bornaviridae). Extraordinary genetic features, including a complex RNA splicing machinery [29, 13], contribute to the outstanding bio
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