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Journal of Neurovirology Feb 2012Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the neurotropic human polyomavirus JC (JCV) lytic... (Review)
Review
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the neurotropic human polyomavirus JC (JCV) lytic infection of oligodendrocytes. PML was first described as a complication of lymphoproliferative disorders more than 50 years ago and emerged as a major complication of human immunodeficiency virus (HIV) infection in the 1980s. Despite the ubiquity of this virus, PML is rare and always seen in association with underlying immunosuppressive condition, such as HIV infection, autoimmune diseases, cancer, and organ transplantation. JCV remains quiescent in the kidneys, where it displays a stable archetypal non-coding control region (NCCR). Conversely, rearranged JCV NCCR, including tandem repeat patterns found in the brain of PML patients, have been associated with neurovirulence. The specific site and mechanism of JCV NCCR transformation is unknown. According to one model, during the course of immunosuppression, JCV departs from its latent state and after entering the brain, productively infects and destroys oligodendrocytes. Although the majority of PML cases occur in severely immunesuppressed individuals, PML has been increasingly diagnosed in patients treated with biological therapies such as monoclonal antibodies (mAbs) that modulate immune system functions: in fact, CD4+ and CD8+ T lymphopenia, resulting from this immunomodulatory therapy, are the primary risk factor. Furthermore, JCV reactivation in nonpermissive cells after treatment with mAbs, such as intestinal epithelial cells in Crohn's disease patients, in association with other host tumor-inducing factors, could provide valid information on the role of JCV in several malignancies, such as colorectal cancer.
Topics: Antibodies, Monoclonal; Biological Therapy; Coinfection; Colorectal Neoplasms; HIV Infections; Humans; Immunocompromised Host; Immunotherapy; JC Virus; Leukoencephalopathy, Progressive Multifocal; Oligodendroglia; Virus Activation
PubMed: 22290500
DOI: 10.1007/s13365-012-0080-7 -
MBio May 2019Extracellular vesicles (EVs) are major vehicles for transporting viruses among hosts. While RNA viruses make up the great majority of transmission by EVs, in a recent...
Extracellular vesicles (EVs) are major vehicles for transporting viruses among hosts. While RNA viruses make up the great majority of transmission by EVs, in a recent article in (mBio 10:e00379-19, 2019, https://mbio.asm.org/content/10/2/e00379-19.long), Morris-Love and colleagues revealed that a double-stranded DNA (dsDNA) virus, JC polyomavirus (JCPyV), a major cause of progressive multifocal leukoencephalopathy (PML), can be released from and transmitted to other glia in EVs. This mode of transmission appears to be highly infectious, independent of the free virus attachment and entry receptors LSTc and 5-HT, and protected from neutralizing antibodies. This novel form of JCPyV transmission may potentially explain its dissemination into the central nervous system (CNS) and its increased virulence.
Topics: Extracellular Vesicles; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Neuroglia; Virus Attachment
PubMed: 31138755
DOI: 10.1128/mBio.01024-19 -
Journal of Neuroimmune Pharmacology :... Dec 2019With the advent of immunomodulatory therapies and the HIV epidemic, the impact of JC Virus (JCV) on the public health system has grown significantly due to the increased... (Review)
Review
With the advent of immunomodulatory therapies and the HIV epidemic, the impact of JC Virus (JCV) on the public health system has grown significantly due to the increased incidence of Progressive Multifocal Leukoencephalopathy (PML). Currently, there are no pharmaceutical agents targeting JCV infection for the treatment and the prevention of viral reactivation leading to the development of PML. As JCV primarily reactivates in immunocompromised patients, it is proposed that the immune system (mainly the cellular-immunity component) plays a key role in the regulation of JCV to prevent productive infection and PML development. However, the exact mechanism of JCV immune regulation and reactivation is not well understood. Likewise, the impact of host factors on JCV regulation and reactivation is another understudied area. Here we discuss the current literature on host factor-mediated and immune factor-mediated regulation of JCV gene expression with the purpose of developing a model of the factors that are bypassed during JCV reactivation, and thus are potential targets for the development of therapeutic interventions to suppress PML initiation. Graphical Abstract.
Topics: Animals; Host Microbial Interactions; Humans; Immunocompromised Host; Immunotherapy; JC Virus; Leukoencephalopathy, Progressive Multifocal; Virus Activation
PubMed: 31452013
DOI: 10.1007/s11481-019-09877-8 -
Cell Cycle (Georgetown, Tex.) Feb 2009Pur-alpha is a ubiquitous multifunctional protein that is strongly conserved throughout evolution, binds to both DNA and RNA and functions in the initiation of DNA... (Review)
Review
Pur-alpha is a ubiquitous multifunctional protein that is strongly conserved throughout evolution, binds to both DNA and RNA and functions in the initiation of DNA replication, control of transcription and mRNA translation. In addition, it binds to several cellular regulatory proteins including the retinoblastoma protein, E2F-1, Sp1, YB-1, cyclin T1/Cdk9 and cyclin A/Cdk2. These observations and functional studies provide evidence that Puralpha is a major player in the regulation of the cell cycle and oncogenic transformation. Puralpha also binds to viral proteins such as the large T-antigen of JC virus (JCV) and the Tat protein of human immunodeficiency virus-1 (HIV-1) and plays a role in the cross-communication of these viruses in the opportunistic polyomavirus JC (JCV) brain infection, progressive multifocal leukoencephalopathy (PML). The creation of transgenic mice with inactivation of the PURA gene that encodes Puralpha has revealed that Puralpha is critical for postnatal brain development and has unraveled an essential role of Puralpha in the transport of specific mRNAs to the dendrites and the establishment of the postsynaptic compartment in the developing neurons. Finally, the availability of cell cultures from the PURA knockout mice has allowed studies that have unraveled a role for Puralpha in DNA repair.
Topics: Acquired Immunodeficiency Syndrome; Animals; Brain; Cell Cycle; Cell Transformation, Neoplastic; DNA Repair; DNA-Binding Proteins; Gene Products, tat; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Neoplasms; Protein Biosynthesis; RNA, Messenger; Transcription Factors
PubMed: 19182532
DOI: 10.4161/cc.8.3.7585 -
Clinical & Developmental Immunology 2012The polyomaviruses are small DNA viruses that can establish latency in the human host. The name polyomavirus is derived from the Greek roots poly-, which means "many,"... (Review)
Review
The polyomaviruses are small DNA viruses that can establish latency in the human host. The name polyomavirus is derived from the Greek roots poly-, which means "many," and -oma, which means "tumours." These viruses were originally isolated in mouse (mPyV) and in monkey (SV40). In 1971, the first human polyomaviruses BK and JC were isolated and subsequently demonstrated to be ubiquitous in the human population. To date, at least nine members of the Polyomaviridae family have been identified, some of them playing an etiological role in malignancies in immunosuppressed patients. Here, we describe the biology of human polyomaviruses, their nonmalignant and malignant potentials ability, and their relationship with the host immune response.
Topics: Animals; BK Virus; Disease Models, Animal; Genome, Viral; Host-Pathogen Interactions; Humans; Immune System; JC Virus; Macaca mulatta; Mice; Neoplasms; Polyomavirus Infections; Simian virus 40; Tumor Virus Infections
PubMed: 22489251
DOI: 10.1155/2012/542092 -
Journal of Virology Jun 2018JC polyomavirus was discovered in 1971, and its name was derived from the initials of the individual from whose brain tissue it was isolated. While most scientists refer...
JC polyomavirus was discovered in 1971, and its name was derived from the initials of the individual from whose brain tissue it was isolated. While most scientists refer to the virus properly, i.e., calling it JCV or JCPyV, there is a small but palpable number of scientists who refer to the virus by the full name of the patient from whom it was isolated. This practice should stop.
Topics: Biomedical Research; Brain; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal
PubMed: 29643238
DOI: 10.1128/JVI.00561-18 -
Revista Da Associacao Medica Brasileira... Nov 2017Few studies directly compare urinary cytology with molecular methods for detecting BK and JC polyomaviruses. Reactivation of BKV infection is the main risk factor for...
Few studies directly compare urinary cytology with molecular methods for detecting BK and JC polyomaviruses. Reactivation of BKV infection is the main risk factor for the development of nephropathy in immunocompromised individuals. The limitation of the cytological method can be attributed to the stage where the infected cell does not have specific and sufficient morphological characteristics for a conclusive diagnosis and can be easily interpreted as degenerative alteration. Moreover, morphologically, it is not possible to differentiate the two types of viruses. Polymerase chain reaction (PCR), not only is a sensitive method, but also allows differentiation of viral types without quantification, and therefore is not indicative of nephropathy. According to the American Society of Nephrology, real-time PCR would be the gold standard to indicate nephropathy because it allows quantifying the number of viral copies.
Topics: BK Virus; DNA, Viral; Humans; JC Virus; Polymerase Chain Reaction; Polyomavirus; Polyomavirus Infections
PubMed: 29451655
DOI: 10.1590/1806-9282.63.11.943 -
Journal of Clinical Virology : the... Apr 2010Polyoma viruses are ubiquitous infecting many different mammalian species including humans. There are five known human polyoma viruses. JC virus and BK virus are two... (Review)
Review
Polyoma viruses are ubiquitous infecting many different mammalian species including humans. There are five known human polyoma viruses. JC virus and BK virus are two polyoma viruses identified nearly three decades ago. Recently WU, KI and Merkel cell polyoma viruses have been isolated from humans. The exact role of these three newly discovered viruses in human disease is not known. Most human polyoma disease is caused by BK and JC viruses which are usually acquired in childhood. Approximately 50-80% of humans have seropositivity to these viruses. Clinically apparent diseases in immunocompetent hosts are extremely rare. These viruses remain latent possibly in the lymphoid organs, neuronal tissue, and kidney and under the circumstances of severe immunosuppression both these viruses reactivate. Neurotropic JC virus reaches the brain and causes progressive multifocal leukoencephalopathy, a demyelinating disease of the central nervous system with a high mortality rate. BK virus is urotheliotropic and its reactivation causes a form of interstitial nephritis, known as BK or polyoma virus associated nephropathy which is associated with high graft loss if not recognized early. There are no known effective antiviral agents for any of the polyoma viruses.
Topics: BK Virus; Humans; Immunocompromised Host; JC Virus; Polyomavirus Infections; Tumor Virus Infections; Viral Tropism; Virus Activation; Virus Latency
PubMed: 20060360
DOI: 10.1016/j.jcv.2009.12.006 -
Seminars in Cancer Biology Aug 2009JC virus (JCV) is a human polyomavirus of the Polyomaviridae family, which also includes BK virus and simian vacuolating virus 40 (SV40). JC virus was first isolated in... (Review)
Review
JC virus (JCV) is a human polyomavirus of the Polyomaviridae family, which also includes BK virus and simian vacuolating virus 40 (SV40). JC virus was first isolated in 1971 from the brain of a patient with Progressive Multifocal Leukoencephalopathy (PML). Like other polyomaviruses, JCV has a restricted host range. The virus infects the majority of the human population with seroconversion occurring during adolescence. JCV has a limited and specific tissue tropism infecting the kidney and oligodendrocytes and astrocytes in the central nervous system (CNS). Initial JCV infection is generally asymptomatic in immunocompetent hosts, and it establishes a persistent infection in the kidney and possibly bone marrow. In immunocompromised individuals JCV can cause a lytic infection in the CNS and lead to development of the fatal, demyelinating disease PML. The name polyoma is derived from the Greek terms: poly, meaning many, and oma, meaning tumors, owing to the capacity of this group of viruses to cause tumors. JCV inoculation of small animal models and non-human primates, which are not permissive to a productive JCV infection, leads to tumor formation. Given the ubiquitous nature of the virus and its strong association with cancer in animal models, it is hypothesized that JCV plays a role in human cancers. However, the role for JCV in human cancers and tumor formation is not clear. Some researchers have reported an association of JCV with human cancers including brain tumors, colorectal cancers, and cancers of the gastrointestinal tract, while other groups report no correlation. Here, we review the role of JCV in cancers in animal models and present the findings on JCV in human cancers.
Topics: Animals; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Neoplasms; Polyomavirus Infections; Tumor Virus Infections
PubMed: 19505654
DOI: 10.1016/j.semcancer.2009.02.013 -
Virus Research Aug 2024The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other...
The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other diseases in immunosuppressed individuals, including granule cell neuronopathy, JCV-associated nephropathy, encephalitis, and meningitis in rare cases. JCV classification is still unclear, where the ICTV (International Committee on Taxonomy of Viruses) has grouped all the strains into human polyomavirus 2, with no classification on clade and subclade levels. Therefore, JCV strains were previously classified using different genomic regions, e.g., full-length, VP1, and the V-T intergenic region etc., and the strains were grouped into several types related to various geographic locations and human ethnicities. However, neither of these classifications and nomenclature contemplates all the groups described so far. Herein, we evaluated all the available full-length coding genomes, VP1, and large T antigen nucleotide sequences of JCV reported during 1993-2023 and classified them into four major phylogenetic clades, i.e., GI-GIV, where GI is further grouped into two types GI.1 and GI.2 with five sub-clades each (GI.1/GI.2 a-e), GII into three (GII a-c), GIII as a separate clade, and GIV into seven sub-clades (GIV a-g). Similarly, the phylogeographic network analysis indicated four major clusters corresponding to GI-GIV clades, each with multiple subclusters and mutational sub-branches corresponding to the subclades. GI and GIV clusters are connected via GI.1-e reported from Europe and America, GII, GIII and GIV clusters are connected by GII-b and GII-c strains reported from Africa, while GIV cluster strains are connected to the Russia-Italy JCV haplotype. Furthermore, we identified JCV-variant-GS/B-Germany-1997 (GenBank ID: AF004350.1) as an inter-genotype recombinant having major and minor parents in the GI.1-e and GII-a clades, respectively. Additionally, the amino acid variability analysis revealed high entropy across all proteins. The large T antigen exhibited the highest variability, while the small t antigen showed the lowest variability. Our phylogenetic and phylogeographic analyses provide a new approach to genotyping and sub-genotyping and present a comprehensive classification system of JCV strains based on their genetic characteristics and geographic distribution, while the genetic recombination and amino acid variability can help identify pathogenicity and develop effective preventive and control measures against JCV infections.
Topics: JC Virus; Phylogeography; Humans; Phylogeny; Genome, Viral; Leukoencephalopathy, Progressive Multifocal; Polyomavirus Infections; Genetic Variation; Cluster Analysis
PubMed: 38848817
DOI: 10.1016/j.virusres.2024.199414