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Molecular Biology and Evolution Feb 2020JC polyomavirus (JCPyV) is one of the most prevalent human viruses. Findings based on the geographic distribution of viral subtypes suggested that JCPyV codiverged with...
JC polyomavirus (JCPyV) is one of the most prevalent human viruses. Findings based on the geographic distribution of viral subtypes suggested that JCPyV codiverged with human populations. This view was however challenged by data reporting a much more recent origin and expansion of JCPyV. We collected information on ∼1,100 worldwide strains and we show that their geographic distribution roughly corresponds to major human migratory routes. Bayesian phylogeographic analysis inferred a Subsaharan origin for JCPyV, although with low posterior probability. High confidence inference at internal nodes provided strong support for a long-standing association between the virus and human populations. In line with these data, pairwise FST values for JCPyV and human mtDNA sampled from the same areas showed a positive and significant correlation. Likewise, very strong relationships were found when node ages in the JCPyV phylogeny were correlated with human population genetic distances (nuclear-marker based FST). Reconciliation analysis detected a significant cophylogenetic signal for the human population and JCPyV trees. Notably, JCPyV also traced some relatively recent migration events such as the expansion of people from the Philippines/Taiwan area into Remote Oceania, the gene flow between North-Eastern Siberian and Ainus, and the Koryak contribution to Circum-Arctic Americans. Finally, different molecular dating approaches dated the origin of JCPyV in a time frame that precedes human out-of-Africa migration. Thus, JCPyV infected early human populations and accompanied our species during worldwide dispersal. JCPyV typing can provide reliable geographic information and the virus most likely adapted to the genetic background of human populations.
Topics: Antarctic Regions; Bayes Theorem; DNA, Mitochondrial; DNA, Viral; Evolution, Molecular; Gene Flow; Human Migration; Humans; JC Virus; Oceania; Philippines; Phylogeography; Polyomavirus Infections; Taiwan
PubMed: 31593241
DOI: 10.1093/molbev/msz227 -
Journal of Clinical Immunology May 2022
Topics: Agammaglobulinemia; Cerebellum; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal
PubMed: 35178641
DOI: 10.1007/s10875-022-01227-3 -
Advances in Experimental Medicine and... 2006Polyomaviruses, as their name indicates, are viruses capable of inducing a variety of tumors in vivo. Members of this family, including the human JC and BK viruses (JCV,... (Review)
Review
Polyomaviruses, as their name indicates, are viruses capable of inducing a variety of tumors in vivo. Members of this family, including the human JC and BK viruses (JCV, BKV), and the better characterized mouse polyomavirus and simian virus 40 (SV40), are small DNA viruses that commandeer a cell's molecular machinery to reproduce themselves. Studies of these virus-host interactions have greatly enhanced our understanding of a wide range of phenomena from cellular processes (e.g., DNA replication and transcription) to viral oncogenesis. The current chapter will focus upon the five known JCV early proteins and the contributions each makes to the oncogenic process (transformation) when expressed in cultured cells. Where appropriate, gaps in our understanding of JCV protein function will be supplanted with information obtained from the study of SV40 and BKV.
Topics: Animals; Antigens, Polyomavirus Transforming; Cell Transformation, Viral; Humans; Immediate-Early Proteins; JC Virus
PubMed: 16626044
DOI: 10.1007/0-387-32957-9_21 -
Molecular characterization of BK and JC viruses circulating among potential kidney donors in Kuwait.BioMed Research International 2013BK and JC polyomaviruses can be associated with nephropathy following renal transplantation. The aim of this study was to determine the prevalence, load, and genotypes...
BK and JC polyomaviruses can be associated with nephropathy following renal transplantation. The aim of this study was to determine the prevalence, load, and genotypes of BK and JC viruses circulated in potential kidney donors in Kuwait. The detection of polyomavirus DNA was carried out in serum and urine samples of 165 potential kidney donors. Seventy (42%) individuals were tested positive for polyomavirus DNA, of whom 20 (12%) had detectable polyomavirus DNA in their serum samples, 40 (24%) in their urine samples, and 10 (6%) in both serum and urine samples. In the group of polyomavirus-positive patients, JC DNA could be detected in 78% of urine samples and 11% of serum samples, whereas BK DNA could be detected in 7% of urine samples and 3% of serum samples. The median polyomaviral load was low. The detected BK sequences in Kuwaiti adults formed new clusters sharing common ancestor with subgroups Ib1 and IVc, which are prevalent in Asia and Europe. Additionally, around half of the detected JCV sequences in Kuwaiti adults formed new clusters within the African subtype 3. Our results suggest high rate of polyomavirus shedding among healthy adults in Kuwait that can jeopardize their suitability for kidney donation.
Topics: Adult; Aged; BK Virus; Base Sequence; DNA, Viral; Female; Humans; JC Virus; Kidney Transplantation; Kuwait; Male; Middle Aged; Tissue Donors
PubMed: 23936831
DOI: 10.1155/2013/683464 -
Medicina Clinica Jan 1996
Review
Topics: BK Virus; Humans; JC Virus; Polyomavirus Infections; Tumor Virus Infections
PubMed: 8948859
DOI: No ID Found -
Journal of Neurovirology 2003JC virus (JCV) is a polyomavirus infecting greater than 80% of the human population early in life. Replication of this virus in oligodendrocytes and astrocytes results... (Review)
Review
JC virus (JCV) is a polyomavirus infecting greater than 80% of the human population early in life. Replication of this virus in oligodendrocytes and astrocytes results in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals, most notably acquired immunodeficiency syndrome (AIDS) patients. Moreover, recent studies have pointed to the association of JCV with a variety of brain tumors, including medulloblastoma. The JCV genome encodes for viral early protein, including large and small T antigens and the newly discovered isoform T', at the early phase of infection and the structural proteins VP1, VP2, and VP3 at the late stage of the lytic cycle. In addition, the late gene is responsible for the production of a small nonstructural protein, agnoprotein, whose function is not fully understood. Here, we have summarized some aspects of the JCV genome structure and function, and its associated diseases, including PML and brain tumors.
Topics: Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal
PubMed: 12709864
DOI: 10.1080/13550280390195360 -
Virology Oct 2023We previously reported the discovery and characterization of two novel proteins (ORF1 and ORF2) generated by the alternative splicing of the JC virus (JCV) late coding...
Human neurotropic polyomavirus, JC virus, late coding region encodes a novel nuclear protein, ORF4, which targets the promyelocytic leukemia nuclear bodies (PML-NBs) and modulates their reorganization.
We previously reported the discovery and characterization of two novel proteins (ORF1 and ORF2) generated by the alternative splicing of the JC virus (JCV) late coding region. Here, we report the discovery and partial characterization of three additional novel ORFs from the same coding region, ORF3, ORF4 and ORF5, which potentially encode 70, 173 and 265 amino acid long proteins respectively. While ORF3 protein exhibits a uniform distribution pattern throughout the cells, we were unable to detect ORF5 expression. Surprisingly, ORF4 protein was determined to be the only JCV protein specifically targeting the promyelocytic leukemia nuclear bodies (PML-NBs) and inducing their reorganization in nucleus. Although ORF4 protein has a modest effect on JCV replication, it is implicated to play major roles during the JCV life cycle, perhaps by regulating the antiviral response of PML-NBs against JCV infections and thus facilitating the progression of the JCV-induced disease in infected individuals.
Topics: Humans; JC Virus; Polyomavirus; Nuclear Proteins; Leukoencephalopathy, Progressive Multifocal; Open Reading Frames; Promyelocytic Leukemia Nuclear Bodies
PubMed: 37741199
DOI: 10.1016/j.virol.2023.109866 -
Neurology Sep 2003
Topics: Acquired Immunodeficiency Syndrome; Adult; Astrocytes; Cerebellum; Child; DNA, Viral; Disease Progression; Humans; Inclusion Bodies, Viral; JC Virus; Leukoencephalopathy, Progressive Multifocal; Neurons; Oligodendroglia; Organ Specificity; Virus Activation; Virus Replication
PubMed: 14504312
DOI: 10.1212/wnl.61.6.734 -
Neurology Aug 2016
Topics: Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Natalizumab
PubMed: 27572430
DOI: 10.1212/WNL.0000000000003081 -
Bioorganic & Medicinal Chemistry Sep 2014Human polyoma- and papillomaviruses are non-enveloped DNA viruses that cause severe pathologies and mortalities. Under circumstances of immunosuppression, JC...
Human polyoma- and papillomaviruses are non-enveloped DNA viruses that cause severe pathologies and mortalities. Under circumstances of immunosuppression, JC polyomavirus causes a fatal demyelinating disease called progressive multifocal leukoencephalopathy (PML) and the BK polyomavirus is the etiological agent of polyomavirus-induced nephropathy and hemorrhagic cystitis. Human papillomavirus type 16, another non-enveloped DNA virus, is associated with the development of cancers in tissues like the uterine cervix and oropharynx. Currently, there are no approved drugs or vaccines to treat or prevent polyomavirus infections. We recently discovered that the small molecule Retro-2(cycl), an inhibitor of host retrograde trafficking, blocked infection by several human and monkey polyomaviruses. Here, we report diversity-oriented syntheses of Retro-2(cycl) and evaluation of the resulting analogs using an assay of human cell infections by JC polyomavirus. We defined structure-activity relationships and also discovered analogs with significantly improved potency as suppressors of human polyoma- and papillomavirus infection in vitro. Our findings represent an advance in the development of drug candidates that can broadly protect humans from non-enveloped DNA viruses and toxins that exploit retrograde trafficking as a means for cell entry.
Topics: Axonal Transport; Cell Line; Dose-Response Relationship, Drug; Humans; JC Virus; Molecular Structure; Neurons; Papillomaviridae; Quinazolines; Structure-Activity Relationship; Virus Internalization
PubMed: 25087050
DOI: 10.1016/j.bmc.2014.06.053