Database and Statistical Analyses of Transcription Factor Binding Sites in the Non-Coding Control Region of JC Virus

JC virus (JCV), as an archetype, establishes a lifelong latent or persistent infection in many healthy individuals. In immunocompromised patients, prototype JCV with variable mutations in the non-coding control region (NCCR) causes progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease. This study was conducted to create a database of NCCR sequences annotated with transcription factor binding sites (TFBSs) and statistically analyze the mutational pattern of the JCV NCCR. JCV NCCRs were extracted from > 1000 sequences registered in GenBank, and TFBSs within each NCCR were identified by computer simulation, followed by examination of their prevalence, multiplicity, and location by statistical analyses. In the NCCRs of the prototype JCV, the limited types of TFBSs, which are mainly present in regions D through F of archetype JCV, were significantly reduced. By contrast, modeling count data revealed that several TFBSs located in regions C and E tended to overlap in the prototype NCCRs. Based on data from the BioGPS database, genes encoding transcription factors that bind to these TFBSs were expressed not only in the brain but also in the peripheral sites. The database and NCCR patterns obtained in this study could be a suitable platform for analyzing JCV mutations and pathogenicity.

Automated summary

This study aimed to create a database of JCV NCCR sequences annotated with TFBSs and statistically analyze the mutational pattern of JCV NCCR. The research found that in the NCCR of prototype JCV, there was a limited variety of TFBSs, with several TFBSs in regions C and E showing an overlapping trend. Data from BioGPS database indicated that genes encoding transcription factors binding to these TFBSs were expressed not only in the brain but also in peripheral sites.