The Borna disease virus (BDV) is an enveloped, negative, non-segmented, single stranded (NNS), RNA virus. It can infect humans, and BDV-infection is associated with neuropsychiatric disorders. Experimental infection of rats with BDV gives mental and behavioral abnormalities, and serves as animal model to study how viruses in general cause diseases of the central nervous system and/or behavioral abnormalities in humans. The RNA genome of BDV has been isolated. Based on the nucleotide sequence, computer analyses predicted the presence of at least five major open reading frames (ORF's). The cDNAs of all the BDV transcripts, especially those of ORF-5, located at the 5' end of the genome and putatively coding for the BDV polymerase (L-protein) have not been cloned. Thus, the regulation of the BDV replicative life-cycle is poorly understood. Based on knowledge of other NNS-RNA viruses, the investigators hypothesized that the minimal replicative unit of BDV in most likely composed of the viral genome tightly associated with thee p40 N-protein (ORF-1), the p24 P/N-protein (ORF-2) and the polymerase protein L coded by ORF-5. ORF-1 and ORF-2 DNA have been cloned into expression vectors. In this pilot study, the investigators will clone the cDNAs of ORF-5 into eukaryotic expression vectors, so that the BDV minimal replicative unit can be reconstructed. Availability of the BDV replicative system will permit the use of site-direct mutageneses to study the proteins and their domains important to the BDV replicative life-cycle. Knowledge of the mechanism(s) whereby BDV replicates will help to design approaches to interfere with BDV replication, and perhaps the pathogeneses of specific BDV-related psychiatric disorders.
| Malik, T H; Kishi, M; Lai, P K (2000) Characterization of the P protein-binding domain on the 10-kilodalton protein of Borna disease virus. J Virol 74:3413-7 |
| Malik, T H; Kobayashi, T; Ghosh, M et al. (1999) Nuclear localization of the protein from the open reading frame x1 of the Borna disease virus was through interactions with the viral nucleoprotein. Virology 258:65-72 |
