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Viruses
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JC Polyomavirus
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JC Polyomavirus

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (31 January 2025) | Viewed by 3355

Special Issue Editors

Dr. Sébastien Lhomme

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Guest Editor
1. Toulouse University Hospital, Purpan Hospital, Virology Department, Toulouse 31300, France
2. Inserm UMR 1291, CNRS UMR5051, Université Toulouse III, Toulouse, France.
Interests: quasi-enveloped viruses; epidemiology; pathogenesis
Special Issues, Collections and Topics in MDPI journals
Dr. Anne-Sophie L'Honneur

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Guest Editor
Department of Virology, Cochin Hospital, AP-HP, 75014 Paris, France
Interests: JC polyomavirus

Special Issue Information

Dear Colleagues,

We are delighted to invite you to contribute to a Special Issue dedicated to JC polyomavirus (JCPyV).

JCPyV, a small, nonenveloped, circular double-stranded DNA virus, was the first of two human polyomaviruses to be isolated in 1971 and was associated with progressive multifocal leukoencephalopathy (PML). PML is a rare, debilitating, and often fatal disease of the central nervous system (CNS) caused by JCPyV, historically described in patients with hematologic malignancies. In the 1980s, the HIV pandemic resulted in a dramatic increase in PML incidence, which significantly decreased with the use of combined antiretroviral therapy. More recently, the wider use of immunomodulatory therapies for chronic inflammatory diseases, organ and stem cell transplantation, has led to iatrogenic PML. To date, no antiviral therapies are available for JCPyV infection.

PML is associated with neurotropic variants harboring rearrangements in the JCPyV genomic regulatory non-coding control region (NCCR), which regulates viral transcription and replication. The mechanisms and the site of emergence of such neurotropic variants are still poorly understood. The absence of robust cell culture systems and animal models and the rarity of the disease allowing studies in large cohorts hampered, at least in part, the understanding of the pathophysiology.

This Special Issue of Viruses focuses on our current knowledge of JC polyomavirus and the direction of future research. We hope to assemble an up-to-date collection of research papers and reviews on JCPyV, its pathophysiology, molecular biology, virus–host interactions, epidemiology, and antiviral development.

We look forward to receiving your contributions.

Dr. Sébastien Lhomme
Dr. Anne-Sophie L’Honneur
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • JC polyomavirus
  • progressive multifocal leukoencephalopathy (PML)
  • neurotropic variants
  • viral genomic rearrangements

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Published Papers (3 papers)

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Research

19 pages, 1457 KiB  
Article
Evaluating Neural Network Performance in Predicting Disease Status and Tissue Source of JC Polyomavirus from Patient Isolates Based on the Hypervariable Region of the Viral Genome
by Aiden M. C. Pike, Saeed Amal, Melissa S. Maginnis and Michael P. Wilczek
Viruses 2025, 17(1), 12; https://doi.org/10.3390/v17010012 - 25 Dec 2024
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Abstract
JC polyomavirus (JCPyV) establishes a persistent, asymptomatic kidney infection in most of the population. However, JCPyV can reactivate in immunocompromised individuals and cause progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease with no approved treatment. Mutations in the hypervariable non-coding control region (NCCR) [...] Read more.
JC polyomavirus (JCPyV) establishes a persistent, asymptomatic kidney infection in most of the population. However, JCPyV can reactivate in immunocompromised individuals and cause progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease with no approved treatment. Mutations in the hypervariable non-coding control region (NCCR) of the JCPyV genome have been linked to disease outcomes and neuropathogenesis, yet few metanalyses document these associations. Many online sequence entries, including those on NCBI databases, lack sufficient sample information, limiting large-scale analyses of NCCR sequences. Machine learning techniques, however, can augment available data for analysis. This study employs a previously compiled dataset of 989 JCPyV NCCR sequences from GenBank with associated patient PML status and viral tissue source to train multilayer perceptrons for predicting missing information within the dataset. The PML status and tissue source models were 100% and 87.8% accurate, respectively. Within the dataset, 348 samples had an unconfirmed PML status, where 259 were predicted as No PML and 89 as PML sequences. Of the 63 sequences with unconfirmed tissue sources, eight samples were predicted as urine, 13 as blood, and 42 as cerebrospinal fluid. These models can improve viral sequence identification and provide insights into viral mutations and pathogenesis. Full article
(This article belongs to the Special Issue JC Polyomavirus)
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12 pages, 1157 KiB  
Article
Performance of Ultrasensitive Polymerase Chain Reaction Testing for JC Polyomavirus in Cerebrospinal Fluid Compared with Pathological Diagnosis of Progressive Multifocal Leukoencephalopathy
by Kenta Takahashi, Kazuo Nakamichi, Yuko Sato, Harutaka Katano, Hideki Hasegawa, Masayuki Saijo and Tadaki Suzuki
Viruses 2024, 16(12), 1950; https://doi.org/10.3390/v16121950 - 19 Dec 2024
Viewed by 647
Abstract
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by the JC polyomavirus (JCPyV). Based on the clinical criteria, PML is diagnosed via polymerase chain reaction (PCR) detection of JCPyV DNA in cerebrospinal fluid (CSF) in combination with neurological and imaging findings. Although [...] Read more.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by the JC polyomavirus (JCPyV). Based on the clinical criteria, PML is diagnosed via polymerase chain reaction (PCR) detection of JCPyV DNA in cerebrospinal fluid (CSF) in combination with neurological and imaging findings. Although the utility of CSF JCPyV testing using ultrasensitive PCR assays has been suggested, its potential requires further evaluation. This study retrospectively analyzed the detection performance of ultrasensitive PCR for CSF JCPyV in patients who underwent brain tissue examination based on the pathological diagnostic criteria for PML. Of the 110 patients with pathologically confirmed definite PML or not PML, standard and ultrasensitive CSF testing was performed for 36 and 74 patients, respectively. The sensitivity of ultrasensitive CSF JCPyV testing of the initial specimens was 85%. With the addition of the follow-up testing, this figure increased to 95%. The specificity and false-positive rate of ultrasensitive CSF JCPyV testing, including follow-up, were 100% and 0%, respectively. No statistically significant correlation was observed between CSF and brain JCPyV levels. The results of this study demonstrate the high sensitivity and accuracy of ultrasensitive CSF JCPyV testing and provide essential information for the clinical diagnosis of PML. Full article
(This article belongs to the Special Issue JC Polyomavirus)
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24 pages, 5428 KiB  
Article
GPCR Inhibitors Have Antiviral Properties against JC Polyomavirus Infection
by Amanda L. Sandberg, Avery C. S. Bond, Lucas J. Bennett, Sophie E. Craig, David P. Winski, Lara C. Kirkby, Abby R. Kraemer, Kristina G. Kelly, Samuel T. Hess and Melissa S. Maginnis
Viruses 2024, 16(10), 1559; https://doi.org/10.3390/v16101559 - 30 Sep 2024
Viewed by 1413
Abstract
JC polyomavirus (JCPyV) infects the majority of the population and initially establishes a persistent but asymptomatic infection of the kidneys. In healthy individuals, the infection remains controlled by the host immune system, but for individuals experiencing prolonged immunosuppression, the infection can reactivate and [...] Read more.
JC polyomavirus (JCPyV) infects the majority of the population and initially establishes a persistent but asymptomatic infection of the kidneys. In healthy individuals, the infection remains controlled by the host immune system, but for individuals experiencing prolonged immunosuppression, the infection can reactivate and spread to the brain, where it causes progressive multifocal leukoencephalopathy (PML), which is a fatal neurodegenerative disease. Currently, there are no approved therapies to treat PML, and affected individuals suffer rapid motor weakness and cognitive deterioration. To identify novel therapeutic treatments for JCPyV infection, receptor agonists/antagonists identified in a previously published drug screen were evaluated for their antiviral properties. Seven drugs were selected and validated using infectivity assays, and the mechanism of inhibition was further explored for G protein coupled receptor (GPCR)-associated inhibitors due to the role of the GPCR 5-hydroxytryptamine 2 receptors (5-HT2Rs) in JCPyV entry. The inhibitors cetirizine and paroxetine both reduced infection early in the JCPyV infectious cycle. Paroxetine specifically reduced viral internalization through altering the receptor density of 5-HT2CR, inhibiting β-arrestin recruitment to the receptor, and reducing MAPK signaling through ERK. These findings highlight the potential of receptor signaling and viral entry mechanisms as possible targets for antiviral drug development. Further, this research suggests that FDA-approved receptor agonists/antagonists currently used to treat other medical conditions could be repurposed into antivirals for the possible treatment of JCPyV infection and the fatal disease PML. Full article
(This article belongs to the Special Issue JC Polyomavirus)
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