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

Kazuo Nakamichi,Toshio Shimokawa

doi:10.3390/v13112314

Kazuo Nakamichi, Toshio Shimokawa

Open Access

https://doi.org/10.3390/v13112314

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Abstract

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.

Highlights

The JC virus (JCV) belongs to the family Polyomaviridae and has a circular doublestranded DNA genome
There was no statistically significant difference in the mean total number of transcription factor binding sites (TFBSs) matrices within either strand of JCV non-coding control region (NCCR) from the urine of healthy subjects and cerebrospinal fluid (CSF) of progressive multifocal leukoencephalopathy (PML) patients. These results indicated that the NCCR of JCV produces complex reconstructions in patients with PML, but that the total number of TFBSs within
The TFBS matrices identified by MatInspector are accompanied by metadata, such as the names and expression patterns of transcription factors that bind to the TFBSs, we found that this information included past designations and obscure expression sites

Summary

Introduction

The JC virus (JCV) belongs to the family Polyomaviridae and has a circular doublestranded DNA genome. JCV is widely distributed in the human population, with 60% to. 80% of adults serologically positive for this virus [1–5]. The first infection with JCV occurs mainly in childhood, after which the virus establishes a persistent asymptomatic infection in the kidney and urinary tract [6,7]. JCV persists or is latent in other sites, such as lymphoid tissue and bone marrow [1,8–11]. This particular JCV presents a stable genomic structure and sequence and is referred to as the archetype [12,13]. Archetype JCV is detected in the urine of 7% to 46% of immunocompetent individuals [4,14–27]

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