Human Polyomavirus JCPyV and Its Role in Progressive Multifocal Leukoencephalopathy and Oncogenesis

Valle, Luis Del; Piña‐Oviedo, Sergio

doi:10.3389/fonc.2019.00711

Cited by 26 publications

(21 citation statements)

References 205 publications

(217 reference statements)

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“…The genotyping results for JCPyV and BKPyV were consistent with those of previously published epidemiological studies, which identified genotypes 1 and I, respectively, as the most represented genotypes within the European population. In addition, the presence of a rearranged NCCR JCPyV infecting PML patients has been widely reported in the literature [52]. The four sequenced BKPyV NCCRs showed different rearrangements and point mutations and were classified arbitrarily as variants of the known Dunlop and TU strains [24].…”

Section: Discussionmentioning

confidence: 99%

Human Polyomaviruses in the Cerebrospinal Fluid of Neurological Patients

Delbue

Franciotta²,

Giannella

et al. 2019

Microorganisms

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Background: Central nervous system (CNS) infections by human polyomaviruses (HPyVs), with the exception of JC (JCPyV), have been poorly studied. Methods: In total, 234 cerebrospinal fluid (CSF) samples were collected from patients affected with neurological disorders. DNA was isolated and subjected to quantitative real-time PCR (Q-PCR) for the detection of six HPyVs: JCPyV, BKPyV, Merkel cell PyV (MCPyV), HPyV6, HPyV7, and HPyV9. Where possible, the molecular characterization of the viral strains was carried out by nested PCR and automated sequencing. Results: JCPyV was detected in 3/234 (1.3%), BKPyV in 15/234 (6.4%), MCPyV in 22/234 (9.4%), and HPyV6 in 1/234 (0.4%) CSF samples. JCPyV was detected at the highest (p < 0.05) mean load (3.7 × 107 copies/mL), followed by BKPyV (1.9 × 106 copies/mL), MCPyV (1.9 × 105 copies/mL), and HPyV6 (3.3 × 104 copies/mL). The noncoding control regions (NCCRs) of the sequenced viral strains were rearranged. Conclusions: HPyVs other than JCPyV were found in the CSF of patients affected with different neurological diseases, probably as bystanders, rather than etiological agents of the disease. However, the fact that they can be latent in the CNS should be considered, especially in immunosuppressed patients.

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Section: Discussionmentioning

confidence: 99%

Human Polyomaviruses in the Cerebrospinal Fluid of Neurological Patients

Delbue

Franciotta²,

Giannella

et al. 2019

Microorganisms

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“…Our work identified the JCV tAg as a type I IFN antagonist that specifically targets the RIG-I signaling pathway. Since polyomavirus tAgs have been most well characterized in their ability to bind to the cellular protein phosphatase 2A (66,67) or for their oncogenic properties (however, not in the case of JCV tAg) (68,69), our study unveiled a novel function for polyomaviral tAg proteins that may play a major role for virus persistence and disease outcomes.…”

Section: Discussionmentioning

confidence: 87%

The Small t Antigen of JC Virus Antagonizes RIG-I-Mediated Innate Immunity by Inhibiting TRIM25’s RNA Binding Ability

Chiang

Dvorkin

Chiang

et al. 2021

mBio

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JC polyomavirus (JCV), a DNA virus that leads to persistent infection in humans, is the causative agent of progressive multifocal leukoencephalopathy, a lethal brain disease that affects immunocompromised individuals. Almost nothing is currently known about how JCV infection is controlled by the innate immune response and, further, whether JCV has evolved mechanisms to antagonize antiviral immunity. Here, we show that the innate immune sensors retinoic acid-inducible gene I (RIG-I) and cGMP-AMP synthase (cGAS) control JCV replication in human astrocytes. We further identify that the small t antigen (tAg) of JCV functions as an interferon (IFN) antagonist by suppressing RIG-I-mediated signal transduction. JCV tAg interacts with the E3 ubiquitin ligase TRIM25, thereby preventing its ability to bind RNA and to induce the K63-linked ubiquitination of RIG-I, which is known to facilitate RIG-I-mediated cytokine responses. Antagonism of RIG-I K63-linked ubiquitination and antiviral signaling is also conserved in the tAg of the related polyomavirus BK virus (BKV). These findings highlight how JCV and BKV manipulate a key innate surveillance pathway, which may stimulate research into designing novel therapies. IMPORTANCE The innate immune response is the first line of defense against viral pathogens, and in turn, many viruses have evolved strategies to evade detection by the host’s innate immune surveillance machinery. Investigation of the interplay between viruses and the innate immune response provides valuable insight into potential therapeutic targets against viral infectious diseases. JC polyomavirus (JCV) is associated with a lifelong, persistent infection that can cause a rare neurodegenerative disease, called progressive multifocal leukoencephalopathy, in individuals that are immunosuppressed. The molecular mechanisms of JCV infection and persistence are not well understood, and very little is currently known about the relevance of innate immunity for the control of JCV replication. Here, we define the intracellular innate immune sensors responsible for controlling JCV infection and also demonstrate a novel mechanism by which a JCV-encoded protein acts as an antagonist of the type I interferon-mediated innate immune response.

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“…Notably, the total number of samples tested for hepatitis A and E. coli was 24, and the total number of samples tested for hepatitis A and total coliforms was 15. The highest correlated indicator for norovirus was polyomavirus ( κ = 0.21), which is a human pathogen that causes progressive multifocal leukoencephalopathy (PML) and thus not a useful environmental indicator organism [ 30 ]. The level of agreement between norovirus with adenovirus was 0.09 ( n = 16, 95% CI −0.05, 0.23) which indicates poor agreement.…”

Section: Resultsmentioning

confidence: 99%

Agricultural Detection of Norovirus and Hepatitis A Using Fecal Indicators: A Systematic Review

Victor

Ellis

Lamar

et al. 2021

International Journal of Microbiology

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Fresh-produce consumers may be at risk of pathogen infection due to fecal contamination of the agricultural environment. Indicators of fecal contamination may be used as a proxy to evaluate the potential presence of human pathogens, such as norovirus and hepatitis A, on agricultural samples. The objective of this systematic review was to determine whether the presence of human norovirus or hepatitis A was associated with microbial indicators in agricultural samples including fresh produce, equipment surfaces, and hands. Four databases (Embase, PubMed, Web of Science, and Agricola) were systematically searched and fifteen articles met inclusion and exclusion criteria. After data extraction, individual indicator-pathogen relationships were assessed using Cohen’s Kappa coefficient. The level of agreement between norovirus with adenovirus was 0.09 (n = 16, 95% CI −0.05, 0.23), indicating poor agreement using Landis and Koch’s criterion. Similarly, the Kappa coefficient between norovirus with E. coli (κ = 0.04, n = 14, 95% CI −0.05, 0.49) or total coliforms (κ = 0.03, n = 4, 95% CI −0.01, 0.02) was also poor. The level of agreement between hepatitis A with adenovirus (κ = −0.03, n = 3, 95% CI −0.06, 0.01) or fecal coliforms (κ = 0, n = 1, 95% CI 0, 0) was also poor. There were moderate relationships between hepatitis A with E. coli (κ = 0.49, n = 3, 95% CI 0.28, 0.70) and total coliforms (κ = 0.47, n = 2, 95% CI 0.47, 0.47). Based on these limited results, common indicator organisms are not strong predictors of the presence of norovirus and hepatitis A virus in the agricultural environment.

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Human Polyomavirus JCPyV and Its Role in Progressive Multifocal Leukoencephalopathy and Oncogenesis

Cited by 26 publications

References 205 publications

Human Polyomaviruses in the Cerebrospinal Fluid of Neurological Patients

Human Polyomaviruses in the Cerebrospinal Fluid of Neurological Patients

The Small t Antigen of JC Virus Antagonizes RIG-I-Mediated Innate Immunity by Inhibiting TRIM25’s RNA Binding Ability

Agricultural Detection of Norovirus and Hepatitis A Using Fecal Indicators: A Systematic Review

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