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Experimental and Clinical... Nov 2020The BK polyomavirus was isolated in 1971; it has been a significant risk factor for both graft dysfunction and failure in renal transplant recipients. So far, no... (Review)
Review
The BK polyomavirus was isolated in 1971; it has been a significant risk factor for both graft dysfunction and failure in renal transplant recipients. So far, no specific treatment option has been available for effective treatment or prophylaxis for BK virus infections. Although the use of heavy immunosuppression has been the main risk factor for BK virus infection, other risk factors are equally important, including elderly recipients, prior rejection episodes, male sex, human leukocyte antigen mismatching, prolonged cold ischemia time, pretransplant BK virus serostatus, and ureteral stenting. Regular follow-up for BK virus infections according to each institution's policy has been, so far, effective in detecting patients with BK virus viremia and consequently preventing allograft loss. The mainstay of management continues to be reduction of immunosuppression. However, newer options are providing new insights, such as cellular immunotherapy. In this review, we will address the diagnosis, screening, new diagnostic tools, and updated management of BK virus infections.
Topics: Adoptive Transfer; Antiviral Agents; BK Virus; Drug Substitution; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Immunotherapy; Kidney Transplantation; Opportunistic Infections; Polyomavirus Infections; Risk Assessment; Risk Factors; Treatment Outcome; Tumor Virus Infections
PubMed: 32552624
DOI: 10.6002/ect.2019.0254 -
Microbiology Spectrum Aug 2016Over the last 10 years, the number of identified polyomaviruses has grown to more than 35 subtypes, including 13 in humans. The polyomaviruses have similar genetic... (Review)
Review
Over the last 10 years, the number of identified polyomaviruses has grown to more than 35 subtypes, including 13 in humans. The polyomaviruses have similar genetic makeup, including genes that encode viral capsid proteins VP1, 2, and 3 and large and small T region proteins. The T proteins play a role in viral replication and have been implicated in viral chromosomal integration and possible dysregulation of growth factor genes. In humans, the Merkel cell polyomavirus has been shown to be highly associated with integration and the development of Merkel cell cancers. The first two human polyomaviruses discovered, BKPyV and JCPyV, are the causative agents for transplant-related kidney disease, BK commonly and JC rarely. JC has also been strongly associated with the development of progressive multifocal leukoencephalopathy (PML), a rare but serious infection in untreated HIV-1-infected individuals and in other immunosuppressed patients including those treated with monoclonal antibody therapies for autoimmune diseases systemic lupus erythematosus, rheumatoid arthritis, or multiple sclerosis. The trichodysplasia spinulosa-associated polyomavirus (TSAPyV) may be the causative agent of the rare skin disease trichodysplasia spinulosa. The remaining nine polyomaviruses have not been strongly associated with clinical disease to date. Antiviral therapies for these infections are under development. Antibodies specific for each of the 13 human polyomaviruses have been identified in a high percentage of normal individuals, indicating a high rate of exposure to each of the polyomaviruses in the human population. PCR methods are now available for detection of these viruses in a variety of clinical samples.
Topics: Antiviral Agents; Diagnostic Tests, Routine; Disease Susceptibility; Drug Discovery; Humans; Immunocompromised Host; Polyomavirus; Polyomavirus Infections; Tumor Virus Infections
PubMed: 27726799
DOI: 10.1128/microbiolspec.DMIH2-0010-2015 -
Viruses Oct 2023JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary... (Review)
Review
JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies of high morbidity and mortality. JCPyV-induced progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease, was an AIDS-defining illness before antiretroviral therapy that has "reemerged" as a complication of immunomodulating and chemotherapeutic agents. No effective anti-polyomavirus therapeutics are currently available. How depressed immune status sets the stage for JCPyV resurgence in the urinary tract, how the virus evades pre-existing antiviral antibodies to become viremic, and where/how it enters the CNS are incompletely understood. Addressing these questions requires a tractable animal model of JCPyV CNS infection. Although no animal model can replicate all aspects of any human disease, mouse polyomavirus (MuPyV) in mice and JCPyV in humans share key features of peripheral and CNS infection and antiviral immunity. In this review, we discuss the evidence suggesting how JCPyV migrates from the periphery to the CNS, innate and adaptive immune responses to polyomavirus infection, and how the MuPyV-mouse model provides insights into the pathogenesis of JCPyV CNS disease.
Topics: Humans; Animals; Mice; Polyomavirus; Leukoencephalopathy, Progressive Multifocal; JC Virus; Polyomavirus Infections; Brain Diseases
PubMed: 37896889
DOI: 10.3390/v15102112 -
Viruses Jan 2020Microtubules, part of the cytoskeleton, are indispensable for intracellular movement, cell division, and maintaining cell shape and polarity. In addition, microtubules... (Review)
Review
Microtubules, part of the cytoskeleton, are indispensable for intracellular movement, cell division, and maintaining cell shape and polarity. In addition, microtubules play an important role in viral infection. In this review, we summarize the role of the microtubules' network during polyomavirus infection. Polyomaviruses usurp microtubules and their motors to travel via early and late acidic endosomes to the endoplasmic reticulum. As shown for SV40, kinesin-1 and microtubules are engaged in the release of partially disassembled virus from the endoplasmic reticulum to the cytosol, and dynein apparently assists in the further disassembly of virions prior to their translocation to the cell nucleus-the place of their replication. Polyomavirus gene products affect the regulation of microtubule dynamics. Early T antigens destabilize microtubules and cause aberrant mitosis. The role of these activities in tumorigenesis has been documented However, its importance for productive infection remains elusive. On the other hand, in the late phase of infection, the major capsid protein, VP1, of the mouse polyomavirus, counteracts T-antigen-induced destabilization. It physically binds microtubules and stabilizes them. The interaction results in the G2/M block of the cell cycle and prolonged S phase, which is apparently required for successful completion of the viral replication cycle.
Topics: Animals; Capsid Proteins; Cell Nucleus; Cytosol; Endoplasmic Reticulum; Endosomes; Host-Pathogen Interactions; Humans; Mice; Microtubules; Polyomavirus; Protein Binding; Virus Replication
PubMed: 31963741
DOI: 10.3390/v12010121 -
The Journal of General Virology Apr 2015Epidemiological studies have suggested that consumption of beef may correlate with an increased risk of colorectal cancer. One hypothesis to explain this proposed link...
Epidemiological studies have suggested that consumption of beef may correlate with an increased risk of colorectal cancer. One hypothesis to explain this proposed link might be the presence of a carcinogenic infectious agent capable of withstanding cooking. Polyomaviruses are a ubiquitous family of thermostable non-enveloped DNA viruses that are known to be carcinogenic. Using virion enrichment, rolling circle amplification (RCA) and next-generation sequencing, we searched for polyomaviruses in meat samples purchased from several supermarkets. Ground beef samples were found to contain three polyomavirus species. One species, bovine polyomavirus 1 (BoPyV1), was originally discovered as a contaminant in laboratory FCS. A previously unknown species, BoPyV2, occupies the same clade as human Merkel cell polyomavirus and raccoon polyomavirus, both of which are carcinogenic in their native hosts. A third species, BoPyV3, is related to human polyomaviruses 6 and 7. Examples of additional DNA virus families, including herpesviruses, adenoviruses, circoviruses and gyroviruses were also detected either in ground beef samples or in comparison samples of ground pork and ground chicken. The results suggest that the virion enrichment/RCA approach is suitable for random detection of essentially any DNA virus with a detergent-stable capsid. It will be important for future studies to address the possibility that animal viruses commonly found in food might be associated with disease.
Topics: Animals; Cattle; Cattle Diseases; Chickens; Food Microbiology; Genome, Viral; Humans; Meat; Molecular Sequence Data; Phylogeny; Polyomavirus; Polyomavirus Infections; Swine
PubMed: 25568187
DOI: 10.1099/vir.0.000033 -
Viruses Jul 2021The BK polyomavirus (BKPyV), a representative of the family Polyomaviridae, is widespread in the human population. While the virus does not cause significant clinical... (Review)
Review
The BK polyomavirus (BKPyV), a representative of the family Polyomaviridae, is widespread in the human population. While the virus does not cause significant clinical symptoms in immunocompetent individuals, it is activated in cases of immune deficiency, both pharmacological and pathological. Infection with the BKPyV is of particular importance in recipients of kidney transplants or HSC transplantation, in which it can lead to the loss of the transplanted kidney or to haemorrhagic cystitis, respectively. Four main genotypes of the virus are distinguished on the basis of molecular differentiation. The most common genotype worldwide is genotype I, with a frequency of about 80%, followed by genotype IV (about 15%), while genotypes II and III are isolated only sporadically. The distribution of the molecular variants of the virus is associated with the region of origin. BKPyV subtype Ia is most common in Africa, Ib-1 in Southeast Asia, and Ib-2 in Europe, while Ic is the most common variant in Northeast Asia. The development of molecular methods has enabled significant improvement not only in BKPyV diagnostics, but in monitoring the effectiveness of treatment as well. Amplification of viral DNA from urine by PCR (Polymerase Chain Reaction) and qPCR Quantitative Polymerase Chain Reaction) is a non-invasive method that can be used to confirm the presence of the genetic material of the virus and to determine the viral load. Sequencing techniques together with bioinformatics tools and databases can be used to determine variants of the virus, analyse their circulation in populations, identify relationships between them, and investigate the directions of evolution of the virus.
Topics: Animals; BK Virus; DNA, Viral; Genetic Variation; Genome, Viral; Genomics; Genotype; Immunocompromised Host; Kidney; Kidney Transplantation; Mice; Oncogenic Viruses; Pathology, Molecular; Polyomavirus Infections; Transplant Recipients; Tumor Virus Infections; Viral Load
PubMed: 34452367
DOI: 10.3390/v13081502 -
Viruses Nov 2017The BK virus (BKPyV) is a member of the family first isolated in 1971. BKPyV causes frequent infections during childhood and establishes persistent infections with... (Review)
Review
The BK virus (BKPyV) is a member of the family first isolated in 1971. BKPyV causes frequent infections during childhood and establishes persistent infections with minimal clinical implications within renal tubular cells and the urothelium. However, reactivation of BKPyV in immunocompromised individuals may cause serious complications. In particular, with the implementation of more potent immunosuppressive drugs in the last decade, BKPyV has become an emerging pathogen in kidney and bone marrow transplant recipients where it often causes associated nephropathy and haemorrhagic cystitis, respectively. Unfortunately, no specific antiviral against BKPyV has been approved yet and the only therapeutic option is a modulation of the immunosuppressive drug regimen to improve immune control though it may increase the risk of rejection. A better understanding of the BKPyV life cycle is thus needed to develop efficient treatment against this virus. In this review, we provide an update on recent advances in understanding the biology of BKPyV.
Topics: Antiviral Agents; BK Virus; Humans; Immunocompromised Host; Immunosuppressive Agents; Polyomavirus Infections; Transplant Recipients; Virus Activation
PubMed: 29099746
DOI: 10.3390/v9110327 -
Reviews in Medical Virology Jul 2020BK polyomavirus (BKPyV or BKV) is a non-enveloped, circular double-stranded DNA virus that may exceed 80% seroprevalence in adults. BKV infection typically occurs during... (Review)
Review
BK polyomavirus (BKPyV or BKV) is a non-enveloped, circular double-stranded DNA virus that may exceed 80% seroprevalence in adults. BKV infection typically occurs during childhood, and the majority of adults are latently infected. While BKV infection is rarely associated with clinical disease in most individuals, in immunosuppressed individuals, reactivation may cause kidney (BK-associated nephropathy) or bladder (hemorrhagic cystitis and ureteral stenosis) injury. No antiviral therapies have been approved for the treatment of BKV infection. Reducing immunosuppression is the most effective therapy, although this is not feasible in many patients. Thus, a robust understanding of viral pathogenesis and viral diversity remains important for the development of future therapeutic strategies. Studies of BKV diversity are quite sparse compared to other common viral infections; thus, much of our understanding of BVK variability and evolution relies heavily analogous studies of other viruses such as HIV or viral hepatitis. We provide a comprehensive review of BKV diversity at the population and individual level with careful consideration of how viral variability may impact viral replication, pathogenesis, tropism, and protein function. We also discuss a number of outstanding questions related to BK virus diversity that should be explored rigorously in future studies.
Topics: Animals; BK Virus; Biodiversity; Evolution, Molecular; Genetic Variation; Genome, Viral; Genomics; Humans; Phylogeny; Polyomavirus Infections
PubMed: 32128960
DOI: 10.1002/rmv.2102 -
Frontiers in Cellular and Infection... 2023The identification of the first human polyomavirus BK (BKV) has been over half century, The previous epidemiological and phylogenetic studies suggest that BKV prevailed... (Review)
Review
The identification of the first human polyomavirus BK (BKV) has been over half century, The previous epidemiological and phylogenetic studies suggest that BKV prevailed and co-evolved with humans, leading to high seroprevalence all over the world. In general, BKV stays latent and symptomless reactivation in healthy individuals. BKV has been mainly interlinked with BKV-associated nephropathy (BKVAN) in kidney-transplant recipients and hemorrhagic cystitis (HC) in hematopoietic stem cell transplant recipients (HSCTRs). However, the mechanisms underlying BKV latency and reactivation are not fully understood and lack of extensive debate. As Merkel cell polyomavirus (MCV) was identified as a pathogenic agent of malignant cutaneous cancer Merkel cell carcinoma (MCC) since 2008, linking BKV to tumorigenesis of urologic tumors raised concerns in the scientific community. In this review, we mainly focus on advances of mechanisms of BKV latency and reactivation, and BKV-associated diseases or tumorigenesis with systematical review of formerly published papers following the PRISMA guidelines. The potential tumorigenesis of BKV in two major types of cancers, head and neck cancer and urologic cancer, was systematically updated and discussed in depth. Besides, BKV may also play an infectious role contributing to HIV-associated salivary gland disease (HIVSGD) presentation. As more evidence indicates the key role of BKV in potential tumorigenesis, it is important to pay more attention on its etiology and pathogenicity and .
Topics: Humans; BK Virus; Phylogeny; Seroepidemiologic Studies; Polyomavirus Infections; Carcinogenesis; Cell Transformation, Neoplastic
PubMed: 37771695
DOI: 10.3389/fcimb.2023.1263983 -
Viruses Mar 2022DNA virus infections are often lifelong and can cause serious diseases in their hosts. Their recognition by the sensors of the innate immune system represents the front... (Review)
Review
DNA virus infections are often lifelong and can cause serious diseases in their hosts. Their recognition by the sensors of the innate immune system represents the front line of host defence. Understanding the molecular mechanisms of innate immunity responses is an important prerequisite for the design of effective antivirotics. This review focuses on the present state of knowledge surrounding the mechanisms of viral DNA genome sensing and the main induced pathways of innate immunity responses. The studies that have been performed to date indicate that herpesviruses, adenoviruses, and polyomaviruses are sensed by various DNA sensors. In non-immune cells, STING pathways have been shown to be activated by cGAS, IFI16, DDX41, or DNA-PK. The activation of TLR9 has mainly been described in pDCs and in other immune cells. Importantly, studies on herpesviruses have unveiled novel participants (BRCA1, H2B, or DNA-PK) in the IFI16 sensing pathway. Polyomavirus studies have revealed that, in addition to viral DNA, micronuclei are released into the cytosol due to genotoxic stress. Papillomaviruses, HBV, and HIV have been shown to evade DNA sensing by sophisticated intracellular trafficking, unique cell tropism, and viral or cellular protein actions that prevent or block DNA sensing. Further research is required to fully understand the interplay between viruses and DNA sensors.
Topics: DNA Virus Infections; DNA, Viral; Herpesviridae; Humans; Immunity, Innate; Polyomavirus
PubMed: 35458396
DOI: 10.3390/v14040666