Borna Disease Virus 1 (BoDV-1): Aktueller Stand und Perspektiven

Abstract

Seit wenigen Jahren kann als gesichert gelten, dass Vertreter der Bornaviren in sehr seltenen Fällen vom Tier auf den Menschen übertragen werden können und in der Folge schwere Gehirnentzündungen auslösen. Ziel ist es, solche Infektionen zu vermeiden, Konzepte für die Behandlung infizierter Personen zu entwickeln und die Verbreitungshäufigkeit im Reservoir möglichst zu minimieren. Dieser Beitrag fasst den aktuellen Stand des Wissens zusammen und adressiert die offenen Fragen.

BoDV-1 Infection in Children and Adolescents: A Systematic Review and Meta-Analysis

“…Borna disease virus 1 (BoDV-1) is a negative sense, single stranded RNA virus that belongs to the family of Bornaviridae (order Mononegavirales) alongside the Borna disease virus 2 (BoDV-2), both from genus Mammalian-1-Orthobornavirus, and the Variegated Squirrel Bornavirus 1 (VSBV-1; genus Mammalian-2-Orthobornavirus) [ 1 , 2 , 3 , 4 ]. The small, highly conservative genome (8.9 kilobases) is enclosed in enveloped viral particles with spherical geometry and helical capsid (70 to 130 nm in diameter for the enveloped particles, and 50 to 60 nm for the viral core) [ 3 , 4 , 5 , 6 ].…”

“…Borna disease virus 1 (BoDV-1) is a negative sense, single stranded RNA virus that belongs to the family of Bornaviridae (order Mononegavirales) alongside the Borna disease virus 2 (BoDV-2), both from genus Mammalian-1-Orthobornavirus, and the Variegated Squirrel Bornavirus 1 (VSBV-1; genus Mammalian-2-Orthobornavirus) [ 1 , 2 , 3 , 4 ]. The small, highly conservative genome (8.9 kilobases) is enclosed in enveloped viral particles with spherical geometry and helical capsid (70 to 130 nm in diameter for the enveloped particles, and 50 to 60 nm for the viral core) [ 3 , 4 , 5 , 6 ]. The viral genome is actively transcribed and replicated in the nucleus of the host cells, which is a quite uncommon feature for RNA viruses [ 4 ], and its six open-reading frames encode at least six proteins: nucleoprotein (N, or p40), phosphoprotein (P, or p24), putative matrix protein (M), type 1 membrane glycoprotein (G), and a putative polymerase (L) [ 7 ].…”

“…The small, highly conservative genome (8.9 kilobases) is enclosed in enveloped viral particles with spherical geometry and helical capsid (70 to 130 nm in diameter for the enveloped particles, and 50 to 60 nm for the viral core) [ 3 , 4 , 5 , 6 ]. The viral genome is actively transcribed and replicated in the nucleus of the host cells, which is a quite uncommon feature for RNA viruses [ 4 ], and its six open-reading frames encode at least six proteins: nucleoprotein (N, or p40), phosphoprotein (P, or p24), putative matrix protein (M), type 1 membrane glycoprotein (G), and a putative polymerase (L) [ 7 ].…”

“…Since 1990, BoDV-1 has been shown as the causative agent of animal Borna disease (BoD) [ 5 , 8 ], a non-purulent, T lymphocyte-mediated meningo-myeloencephalitis characterized by movement disorders and behavioral abnormalities, including increased aggressivity, with a high case-fatality ratio [ 1 , 2 , 9 , 10 , 11 , 12 , 13 ]. BoD was originally described in nineteenth century as an epidemic disease of domestic mammals and livestock (mostly horses and sheep) from Southern Germany, Liechtenstein, Switzerland, and Austria [ 1 , 2 , 4 , 9 , 10 , 11 , 12 , 13 ]. A putative reservoir host for BoDV-1 has been recently suggested in Crocidura leucodon [ 9 ], the bicolored white-toother shrew, a small insectivore from the family of Soricidae [ 3 , 12 , 14 , 15 ], because of its high tolerance to BoDV-1 infection [ 9 ].…”

“…On the one hand, seroprevalence for BoDV-1 antibodies was identified in areas outside the known distribution of Crocidura leucodon , such as Japan [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], Thailand [ 35 ], Australia [ 36 ], Mexico [ 37 ], and the United States [ 25 , 38 ]. On the other hand, BoDV-1 antibodies have been described as scarcely specific [ 39 ], with a considerable suspicion that the earlier studies may have been affected by high rates of false positive results due to cross-reactivity with other pathogens [ 3 , 4 ] or even a laboratory contamination of samples [ 3 , 5 ]. However, subsequent molecular and biological analyses have dismissed the aforementioned assumptions [ 40 , 41 ]: even though an earlier meta-analysis of putative human BoDV-1 sequences failed to provide evidence implicating a causal role of BoDV-1 in mental illnesses [ 42 ], a recent meta-analysis has suggested that BoDV-1 infections may be associated with a substantially increased risk of schizophrenia (Odds Ratio [OR] 3.83, 95% Confidence Interval [95% CI] 1.59 to 9.20 for estimates based on Real Time Polymerase Chain Reaction [RT-PCR]) [ 23 ].…”