Project description:Borna disease virus (BDV) is a highly neurotropic negative-strand RNA virus that belongs to the Mononegavirales. Many reports demonstrated that natural infection of BDV occurs worldwide in a variety of vertebrate species, suggesting that host range of this virus includes all warm-blooded animals. BDV persistently infects the central nervous system (CNS) of many animal species and causes neurobehavioral disorders resembling autism, such as anxiety, aggression, hyperactivity, abnormal play behavior, and cognitive deficits. We previously reported the generation of transgenic mice expressing BDV phosphoprotein (P) selectively in astrocytes. This transgenic mouse, P-Tg, showed striking neurobehavioral abnormalities resembling those in BDV-infected animals, such as enhanced intermale aggressiveness, hyperactivity and spatial reference memory deficit. To reveal the molecular mechanisms how glial cells induce these abnormalities, we performed microarray analysis using C6 rat glioma cells expressing either GFP (C6-GFP) or BDV P (C6-P). Sixty-eight genes are significantly affected in C6-P cells. The genes, whose products are localized at the extracellular region, were enriched in the differentially expressed genes in C6-P cells. Furthermore, gene ontology analysis revealed an emphasis on genes involved in morphogenesis. It is highly likely that the secretion of astrocyte factors may be widely dysregulated in the P-Tg, leading to the astrocyte hypofunction in the brain.
Project description:Borna disease virus is a neurotropic negative-strand RNA virus that infects a wide range of vertebrate hosts, causing disturbances in movement and behavior. We have cloned and sequenced the 8910-nucleotide viral genome by using RNA from Borna disease virus particles. The viral genome has complementary 3' and 5' termini and contains antisense information for five open reading frames. Homology to Filoviridae, Paramyxoviridae, and Rhabdoviridae is found in both cistronic and extracistronic regions. Northern analysis indicates that the virus transcribes mono- and polycistronic RNAs and uses termination/polyadenylylation signals reminiscent of those observed in other negative-strand RNA viruses. Borna disease virus is likely to represent a previously unrecognized genus, bornaviruses, or family, Bornaviridae, within the order Mononegavirales.
Project description:We developed a novel approach combining next generation sequencing, bioinformatics and mass spectrometry to assess the impact of non-MHC polymorphisms on the repertoire of MHC I-associated peptides (MIPs). We compared the genomic landscape of MIPs eluted from B lymphoblasts of two MHC-identical siblings and determined that MIPs mirror the genomic frequency of non-synonymous polymorphisms but they behave as recessive traits at the surface level. Moreover, we showed that 11.7% of the MIP coding exome is polymorphic at the population level. Our method provides fundamental insights into the relation between the genomic self and the immune self and accelerates the discovery of polymorphic MIPs (also known as minor histocompatibility antigens), which play a major role in allo-immune responses.
Project description:We developed a novel approach combining next generation sequencing, bioinformatics and mass spectrometry to assess the impact of non-MHC polymorphisms on the repertoire of MHC I-associated peptides (MIPs). We compared the genomic landscape of MIPs eluted from B lymphoblasts of two MHC-identical siblings and determined that MIPs mirror the genomic frequency of non-synonymous polymorphisms but they behave as recessive traits at the surface level. Moreover, we showed that 11.7% of the MIP coding exome is polymorphic at the population level. Our method provides fundamental insights into the relation between the genomic self and the immune self and accelerates the discovery of polymorphic MIPs (also known as minor histocompatibility antigens), which play a major role in allo-immune responses. RNA-seq of human B lymphoblasts derived from peripheral blood mononuclear cells from 2 HLA-identical female siblings.