Acquisition of Borna disease virus virulence by in vivo evolution

博尔纳病病毒（Borna disease virus，BDV）是一种嗜神经性包膜病毒，基因组为不分节段、单链和负链RNA。我们已经报道了BDV在日本动物如马、羊、牛和猫中的分布。此外，我们已经报道，与献血者相比，精神分裂症和慢性疲劳综合征患者的BDV患病率显著较高。本研究对人脑中BDV的可能性进行了研究，结果如下：（1）在4例精神分裂症患者尸检脑组织中，有1例在海马、脑桥和小脑中检测到BDV RNA。相反，在来自2个尸检的健康脑的几个脑区域中没有阳性病例。2）我们通过将这些脑区域接种到新生沙鼠，然后将沙鼠脑与人少突胶质细胞瘤衍生的细胞系共培养，从BDV RNA阳性的海马和小脑分离人BDV。3)测定了1例精神分裂症患者脑组织BDV的全长核苷酸序列，并与马脑组织BDV的核苷酸序列进行了比较，发现人BDV与马BDV在核苷酸水平上的同源性约为98%。尤其是磷蛋白（p24）和糖蛋白（gp56）有许多氨基酸取代。4)我们已经研究了帕金森病患者黑质中BDV RNA的可能检测。A医院4只和B医院5只中分别有3只和3只BDV RNA阳性。新生沙鼠脑内接种BDV RNA阳性的黑质也有BDV RNA阳性。然而，我们不能检测到BDV复制人少突胶质细胞瘤衍生的细胞系，虽然我们检查了在相同的条件下，在BDV分离从大脑中的精神分裂症患者。

Borna disease virus (BDV) is neurotropic envelope virus with nonsegmented, single-stranded and minus-stranded RNA as a genome. We have reported that BDV is distributed in Japanese animals such as horses, sheep, cattle and cats. Further, we have reported that BDV prevalence was significantly higher in patients with schizophrenia and chronic fatigue syndrome, compared with blood donors. In this study, we have worked on the possible identification of a virulent BDV in human brains and obtained results as follows :1) We detected BDV RNA in hippocampus, pons and cerebellum in one among four autopsied brains derived from schizophrenia patients. In contrast, there are no positive cases in several brain regions examined which were derived from 2 autopsied healthy brains.2) We isolated human BDV from BDV RNA-positive hippocampus and cerebellum by inoculation of these brain regions to newborn gerbils followed by co-culture of the gerbil brain with human oligodendroglioma-derived cell line. 3) Full-length nucleotide sequence of BDV derived from the brain of a patient with schizophrenia was determined and compared with that of horse brain-derived BDV.The homology of human BDV with horse BDV at nucleotide sequence level was about 98%. Especially, the phosphoprotein (p24) and glycoprotein (gp 56) had many ammo acid substitutions. 4) We have examined the possible detection of BDV RNA in substantia nigra from patients with Parkinson's disease. Three among four from A hospital and three among 5 from B hospital were positive for BDV RNA BDV RNA was also positive in newborn gerbils intracranially inoculated with these BDV RNA-positive substantia nigras. However, we could not detect BDV replication in human oligodendroglioma-derived cell line, although we examined under the same conditions as in BDV isolation from the brain of a patient with schizophrenia.