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Journal of Neurovirology Feb 2023The diagnosis of progressive multifocal leukoencephalopathy (PML) is based on a combination of clinical, radiographic, and laboratory findings. However, negative JC... (Review)
Review
The diagnosis of progressive multifocal leukoencephalopathy (PML) is based on a combination of clinical, radiographic, and laboratory findings. However, negative JC polyomavirus (JCPyV) PCR in CSF does not always rule out JCPyV-related PML. In this narrative review, we sought to examine the characteristic of biopsy-proven PML in patients with undetectable JCPyV CSF PCR and provide alternative approaches in this scenario.
Topics: Humans; Leukoencephalopathy, Progressive Multifocal; JC Virus; Polymerase Chain Reaction
PubMed: 36723823
DOI: 10.1007/s13365-023-01113-7 -
Journal of Cellular Physiology Oct 2016Agnoprotein is an important regulatory protein of polyomaviruses, including JCV, BKV, and SV40. In the absence of its expression, these viruses are unable to sustain... (Review)
Review
Agnoprotein is an important regulatory protein of polyomaviruses, including JCV, BKV, and SV40. In the absence of its expression, these viruses are unable to sustain their productive life cycle. It is a highly basic phosphoprotein that localizes mostly to the perinuclear area of infected cells, although a small amount of the protein is also found in nucleus. Much has been learned about the structure and function of this important regulatory protein in recent years. It forms highly stable dimers/oligomers in vitro and in vivo through its Leu/Ile/Phe-rich domain. Structural NMR studies revealed that this domain adopts an alpha-helix conformation and plays a critical role in the stability of the protein. It associates with cellular proteins, including YB-1, p53, Ku70, FEZ1, HP1α, PP2A, AP-3, PCNA, and α-SNAP; and viral proteins, including small t antigen, large T antigen, HIV-1 Tat, and JCV VP1; and significantly contributes the viral transcription and replication. This review summarizes the recent advances in the structural and functional properties of this important regulatory protein. J. Cell. Physiol. 231: 2115-2127, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Chromobox Protein Homolog 5; Humans; JC Virus; Polyomavirus; Polyomavirus Infections; Transcription Factors; Viral Proteins; Viral Regulatory and Accessory Proteins
PubMed: 26831433
DOI: 10.1002/jcp.25329 -
Developments in Biological... 1998The two human polyomaviruses JC and BK are ubiquitous in the human population. Primary infection leads to lifelong persistence in the kidney, the CNS and in lymphoid... (Review)
Review
The two human polyomaviruses JC and BK are ubiquitous in the human population. Primary infection leads to lifelong persistence in the kidney, the CNS and in lymphoid cells. Virus is shed into the urine and is transmitted at least in part by the oral route. Under limited changes of the immunological state persistent polyomavirus infection is activated to an asymptomatic virus production. However, in severe long-lasting immunosuppression, highly effective virus multiplication can be accompanied by extended cytolytic damage of viral target cells leading to fatal disease. Whereas BKV is associated with severe urogenital disorders, JCV affects the CNS, leading to progressive multifocal leukoencephalopathy (PML). Although the number of PML cases is steadily increasing because of the AIDS epidemic, the mechanisms responsible for the change from asymptomatic-activated to the diseased state are not yet understood. As a possible pathogenic factor, the role of genomic heterogeneity of the transcriptional control region in the induction of disease is discussed.
Topics: BK Virus; DNA, Viral; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Tumor Virus Infections
PubMed: 9776228
DOI: No ID Found -
Forensic Science International. Genetics Mar 2008Increasing numbers of unidentified cadavers have recently become an important forensic problem in many countries. To identify such cadavers, DNA typing method is widely... (Review)
Review
Increasing numbers of unidentified cadavers have recently become an important forensic problem in many countries. To identify such cadavers, DNA typing method is widely used. However, as this technique requires reference DNA samples, a method that would quickly narrow down possible candidates for the cadavers is needed to enable rapid identification. Unfortunately, no really reliable methods suitable for this purpose have been available; however, methods using the human parasites, JC virus, BK virus and EB virus, have been reported. These new methods narrow down the candidates by elucidating geographic origins. Though not detectable in all cases, results using such methods with several parasites have enabled us to estimate geographic origins of unidentified cadavers with a high detection rate.
Topics: BK Virus; Cadaver; DNA Fingerprinting; DNA, Viral; Forensic Anthropology; Genotype; Geography; Humans; JC Virus; Oligonucleotide Array Sequence Analysis; Reference Standards
PubMed: 19083803
DOI: 10.1016/j.fsigen.2007.10.184 -
Expert Opinion on Biological Therapy Sep 2011As a viral gene delivery vector, the recombinant JC virus-like particles (VLPs) can be easily generated in large quantities and at low cost. Exogenous genes of interest... (Review)
Review
INTRODUCTION
As a viral gene delivery vector, the recombinant JC virus-like particles (VLPs) can be easily generated in large quantities and at low cost. Exogenous genes of interest can be packaged by the VLP without the involvement of viral genetic material and then delivered into any tissue susceptible to JC virus (JCV) to allow gene transduction. Therefore, it should be possible in the future to develop a gene delivery vector using the human JC VLPs that will allow gene therapy.
AREAS COVERED
Development of a gene delivery vector using the polyomavirus VLPs is reviewed in this article. The advantages and disadvantages of using JC VLP for gene delivery are discussed.
EXPERT OPINION
Human JC VLPs are readily produced and can be engineered with ease; they allow specific targeting without the presence of any viral genetic material. For therapeutic purposes, gene(s) of interest or other compounds can be packaged into the VLP and delivered to JCV-susceptible cells at high efficiency.
Topics: Animals; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans; JC Virus; Neoplasms; Virion
PubMed: 21554145
DOI: 10.1517/14712598.2011.583914 -
Annals of Neurology Dec 2014
Topics: Animals; Antibodies, Viral; Humans; JC Virus; Viral Load
PubMed: 25380145
DOI: 10.1002/ana.24302 -
Journal of Peptide Science : An... Mar 2015The JC polyomavirus (JCPyV) infects approximately 50% of the human population. In healthy individuals, the infection remains dormant and asymptomatic, but in...
The JC polyomavirus (JCPyV) infects approximately 50% of the human population. In healthy individuals, the infection remains dormant and asymptomatic, but in immuno-suppressed patients, it can cause progressive multifocal leukoencephalopathy (PML), a potentially fatal demyelinating disease. Currently, there are no drugs against JCPyV infection nor for the treatment of PML. Here, we report the development of small-molecule inhibitors of JCPyV that target the initial interaction between the virus and host cell and thereby block viral entry. Utilizing a combination of computational and NMR-based screening techniques, we target the LSTc tetrasaccharide binding site within the VP1 pentameric coat protein of JCPyV. Four of the compounds from the screen effectively block viral infection in our in vitro assays using SVG-A cells. For the most potent compound, we used saturation transfer difference NMR to determine the mode of binding to purified pentamers of JCPyV VP1. Collectively, these results demonstrate the viability of this class of compounds for eventual development of JCPyV-antiviral therapeutics.
Topics: Animals; Antiviral Agents; Binding Sites; Biological Assay; COS Cells; Capsid Proteins; Cell Line, Transformed; Chlorocebus aethiops; Escherichia coli; Gene Expression; HEK293 Cells; Humans; JC Virus; Molecular Docking Simulation; Neuroglia; Protein Binding; Protein Multimerization; Recombinant Proteins; Small Molecule Libraries; Virus Internalization
PubMed: 25522925
DOI: 10.1002/psc.2731 -
Uirusu 2015Viroporins are small and hydrophobic viral proteins that form pores on host cell membranes, and their expression can increase the permeability of cellular membranes and... (Review)
Review
Viroporins are small and hydrophobic viral proteins that form pores on host cell membranes, and their expression can increase the permeability of cellular membranes and the production of progeny virus particles. JC virus (JCV) is the causative agent of progressive multifocal leukoenchephalopathy (PML). We demonstrate that JCV Agno, which is the small and hydrophobic protein, andincreases the plasma membrane permeability and virion release, acts as a viroporin. We also demonstrate that an interaction of Agno with a host cellular protein regulates the viroporin activity of Agno. These findings indicate a new paradigm in virus-host interactions regulating viroporin activity and viral replication.
Topics: Cell Membrane Permeability; Host-Pathogen Interactions; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Membrane Lipids; Viral Regulatory and Accessory Proteins; Virion; Virus Replication
PubMed: 26923968
DOI: 10.2222/jsv.65.135 -
Current Opinion in Neurology Jun 2011The appearance of progressive multifocal leukoencephalopathy (PML) in association with newer, highly effective biological agents has increased the importance of...
PURPOSE OF REVIEW
The appearance of progressive multifocal leukoencephalopathy (PML) in association with newer, highly effective biological agents has increased the importance of understanding the mechanisms by which they and other underlying predisposing causes give rise to the disorder. This review attempts to describe what is currently known about the pathogenesis of PML.
RECENT FINDINGS
JC virus is a ubiquitous polyoma virus that infects at least 50% of the human population by adulthood. Despite this high prevalence of infection PML remains exceptionally rare, suggesting the presence of multiple high barriers to its development. Proposed barriers include host, viral, and immunological factors. With respect to host factors, no data is presently available. A viral barrier exists if the initial infection is with the archetype JC virus which requires genetic rearrangement of its promoter region to enable effective replication in oligodendrocytes. Cell-mediated immunity, in particular, JC virus-specific cytotoxic T cells, appears to be the most important recognized immunological barrier but likely not the only one.
SUMMARY
There remain significant gaps in our understanding of JC virus biology and PML pathogenesis. However, the present state of knowledge provides a framework for the generation of coherent and reasonable hypotheses. A better understanding of these disease mechanisms will improve our ability to both predict and mitigate the risks for the development of PML associated with various predisposing diseases and therapies.
Topics: Animals; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Models, Immunological
PubMed: 21499097
DOI: 10.1097/WCO.0b013e328346d2a3 -
Science Translational Medicine Sep 2015JC polyomavirus (JCV) persistently infects the urinary tract of most adults. Under conditions of immune impairment, JCV causes an opportunistic brain disease,...
JC polyomavirus (JCV) persistently infects the urinary tract of most adults. Under conditions of immune impairment, JCV causes an opportunistic brain disease, progressive multifocal leukoencephalopathy (PML). JCV strains found in the cerebrospinal fluid of PML patients contain distinctive mutations in surface loops of the major capsid protein, VP1. We hypothesized that VP1 mutations might allow the virus to evade antibody-mediated neutralization. Consistent with this hypothesis, neutralization serology revealed that plasma samples from PML patients neutralized wild-type JCV strains but failed to neutralize patient-cognate PML-mutant JCV strains. This contrasted with serological results for healthy individuals, most of whom robustly cross-neutralized all tested JCV variants. Mice administered a JCV virus-like particle (VLP) vaccine initially showed neutralizing "blind spots" (akin to those observed in PML patients) that closed after booster immunization. A PML patient administered an experimental JCV VLP vaccine likewise showed markedly increased neutralizing titer against her cognate PML-mutant JCV. The results indicate that deficient humoral immunity is a common aspect of PML pathogenesis and that vaccination may overcome this humoral deficiency. Thus, vaccination with JCV VLPs might prevent the development of PML.
Topics: Humans; Immune Evasion; JC Virus; Mutation; Neutralization Tests; Viral Vaccines
PubMed: 26400912
DOI: 10.1126/scitranslmed.aab1720