12/12/2023 0 Comments Duolink image toolImmune-mediated pathological processes are considered to lead to the development of clinical signs in infected animals ( Stitz et al., 1995). Despite recent progress, the pathogenesis of bornavirus infections is poorly understood. Nuclear replication, however, characterizes a unique feature of Bornaviridae ( Cubitt and Torre, 1994), involving intense shuttling of proteins between nuclear and cytoplasmic compartments. 8.9 kb) constitutes a non-segmented, single-stranded RNA of negative polarity with six open reading frames (ORFs) encoding the nucleoprotein (N), phosphoprotein (P), a small non-structural protein (X), matrix protein (M), glycoprotein (G) and the RNA-dependent RNA-polymerase (L), a genome organization similar to that of other Mononegavirales ( Lipkin and Briese, 2006). Moreover, variegated squirrel 1 bornavirus (VSBV-1) was recently proposed to underlie three cases of fatal viral encephalitis in human ( Hoffm ann et al., 2015). These findings could point to a relationship of BDV infections and psychiatric diseases ( Feschotte, 2010), as has been previously suggested ( Bode and Ludwig, 2003). Some of the EBLNs found in the human genome are conserved as protein-coding genes ( Belyi et al., 2010 Horie et al., 2010). Endogenous bornavirus N-like elements (EBLNs) resembling the N-gene of BDV were found in the genomes of humans, primates, and other mammal species ( Belyi et al., 2010 Horie et al., 2010), suggesting that bornaviruses are evolutionarily old viruses, co-existing with humans and their predecessors for a long time. Human isolates have been reported from Germany ( Bode et al. They have been shown to cause neurological diseases in a wide range of mammals, including Borna disease in horses and sheep ( Lipkin and Briese, 2006 Ludwig et al., 1988), as well as staggering disease in cats ( Wensman et al., 2014). All variants/strains are characterized by highly conserved genomes, persistently infecting neurons and glia cells mainly in the central nervous system (CNS). This work, however, focuses on classical Borna disease virus type 1 (BDV genus Bornavirus, species Mammalian 1 bornavirus). Psittaciform and passeriform bornaviruses cause proventricular dilatation disease (PDD) in psittacine and non-psittacine birds ( Kistler et al., 2008 Weissenböck et al., 2009). T he family Bornaviridae of the order Mononegavirales has currently been taxonomically reorganized to allow for classifying numerous new viruses discovered in various bird species, which are genetically different from mammalian bornavirus ( Kuhn et al., 2015). In this study, we have for the first time directly visualized protein-protein interactions between BDV and its host, and thereby confirmed previous data to demonstrate findings in cell cultures to be applicable also in experimentally and naturally infected animals. BDV proteins and their interactions with host proteins could be shown in cell cultures (HMGB1, Cdc2) and in brain tissues of rat (HMGB1, Cdc2) and horse (Cdc2 only) infected with BDV. Finally, protein-protein interactions were visualized in both C6BV and brain tissues of experimentally as well as naturally infected animals (rat and horse, respectively). Next, in situ PLA was applied to detect BDV P in brain tissues of infected animals. First, we used rat glioma cell cultures persistently infected with a laboratory strain of BDV (C6BV) to establish the assay. In this study, we focused on some of these interactions (BDV P-HMGB1, BDV N/P-Cdc2). BDV P (phosphoprotein) and N (nucleoprotein) have previously been reported to interact with several host proteins, thereby interfering with various signaling pathways. Here we have used in situ proximity ligation assay ( in situ PLA), a selective tool for studying virus-host protein-protein interactions. Viral persistence in the brain has been frequently observed, however, the exact mechanisms behind BDV’s ability to establish persistence despite a prominent immune response are not known. Abstract | Borna disease virus type 1 (BDV) comprises highly conserved neurotropic non-segmented negative strand RNA-virus variants causing neurological and behavioral disorders in a wide range of mammalian animals, possibly including humans.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |