Rearrangement in the Hypervariable Region of JC Polyomavirus Genomes Isolated from Patient Samples and Impact on Transcription Factor-Binding Sites and Disease Outcomes

Wilczek, Michael P.; Pike, Aiden M. C.; Craig, Sophie E.; Maginnis, Melissa S.; King, Benjamin L.

doi:10.3390/ijms23105699

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Rearrangement in the Hypervariable Region of JC Polyomavirus Genomes Isolated from Patient Samples and Impact on Transcription Factor-Binding Sites and Disease Outcomes

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Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469, USA

Graduate School in Biomedical Science and Engineering, University of Maine, Orono, ME 04469, USA

Authors to whom correspondence should be addressed.

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Present Address: The Roux Institute, Northeastern University, Portland, ME 04101, USA.

Academic Editor: Gabriel Santpere

Int. J. Mol. Sci. 2022, 23(10), 5699; https://doi.org/10.3390/ijms23105699

Received: 7 April 2022 / Revised: 13 May 2022 / Accepted: 16 May 2022 / Published: 20 May 2022

(This article belongs to the Special Issue The Role of Genetic Variation on Transcription Factor Binding Sites in Evolution and Disease)

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Abstract

JC polyomavirus (JCPyV) is the causative agent of the fatal, incurable, neurological disease, progressive multifocal leukoencephalopathy (PML). The virus is present in most of the adult population as a persistent, asymptotic infection in the kidneys. During immunosuppression, JCPyV reactivates and invades the central nervous system. A main predictor of disease outcome is determined by mutations within the hypervariable region of the viral genome. In patients with PML, JCPyV undergoes genetic rearrangements in the noncoding control region (NCCR). The outcome of these rearrangements influences transcription factor binding to the NCCR, orchestrating viral gene transcription. This study examines 989 NCCR sequences from patient isolates deposited in GenBank to determine the frequency of mutations based on patient isolation site and disease status. The transcription factor binding sites (TFBS) were also analyzed to understand how these rearrangements could influence viral transcription. It was determined that the number of TFBS was significantly higher in PML samples compared to non-PML samples. Additionally, TFBS that could promote JCPyV infection were more prevalent in samples isolated from the cerebrospinal fluid compared to other locations. Collectively, this research describes the extent of mutations in the NCCR that alter TFBS and how they correlate with disease outcome. View Full-Text

Keywords: JC polyomavirus; transcription factors; mutations; viral genome; PML; NCCR

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MDPI and ACS Style

Wilczek, M.P.; Pike, A.M.C.; Craig, S.E.; Maginnis, M.S.; King, B.L. Rearrangement in the Hypervariable Region of JC Polyomavirus Genomes Isolated from Patient Samples and Impact on Transcription Factor-Binding Sites and Disease Outcomes. Int. J. Mol. Sci. 2022, 23, 5699. https://doi.org/10.3390/ijms23105699

AMA Style

Wilczek MP, Pike AMC, Craig SE, Maginnis MS, King BL. Rearrangement in the Hypervariable Region of JC Polyomavirus Genomes Isolated from Patient Samples and Impact on Transcription Factor-Binding Sites and Disease Outcomes. International Journal of Molecular Sciences. 2022; 23(10):5699. https://doi.org/10.3390/ijms23105699

Chicago/Turabian Style

Wilczek, Michael P., Aiden M. C. Pike, Sophie E. Craig, Melissa S. Maginnis, and Benjamin L. King. 2022. "Rearrangement in the Hypervariable Region of JC Polyomavirus Genomes Isolated from Patient Samples and Impact on Transcription Factor-Binding Sites and Disease Outcomes" International Journal of Molecular Sciences 23, no. 10: 5699. https://doi.org/10.3390/ijms23105699

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Rearrangement in the Hypervariable Region of JC Polyomavirus Genomes Isolated from Patient Samples and Impact on Transcription Factor-Binding Sites and Disease Outcomes

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