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Viruses Jul 2022BK virus maintains a latent infection that is ubiquitous in humans. It has a propensity for reactivation in the setting of a dysfunctional cellular immune response and... (Review)
Review
BK virus maintains a latent infection that is ubiquitous in humans. It has a propensity for reactivation in the setting of a dysfunctional cellular immune response and is frequently encountered in kidney transplant recipients. Screening for the virus has been effective in preventing progression to nephropathy and graft loss. However, it can be a diagnostic and therapeutic challenge. In this in-depth state-of-the-art review, we will discuss the history of the virus, virology, epidemiology, cellular response, pathogenesis, methods of screening and diagnosis, evidence-based treatment strategies, and upcoming therapeutics, along with the issue of re-transplantation in patients.
Topics: BK Virus; Humans; Kidney Transplantation; Polyomavirus Infections; Tumor Virus Infections; Viremia
PubMed: 35893681
DOI: 10.3390/v14081616 -
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 -
Viruses Apr 2021As guest editors, we are pleased to present this Special Issue on BK virus (BKV) and transplantation with the intention of exploring some aspects related to...
As guest editors, we are pleased to present this Special Issue on BK virus (BKV) and transplantation with the intention of exploring some aspects related to BKV-associated diseases in transplant recipients, since they are still unclear [...].
Topics: BK Virus; Disease Susceptibility; Humans; Kidney Transplantation; Organ Transplantation; Polyomavirus Infections; Transplant Recipients; Tumor Virus Infections
PubMed: 33922350
DOI: 10.3390/v13050733 -
Dermatologic Clinics Jan 2023Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma that typically presents as a rapidly enlarging violaceous papulonodule on sun-damaged skin in elderly patients.... (Review)
Review
Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma that typically presents as a rapidly enlarging violaceous papulonodule on sun-damaged skin in elderly patients. MCC has high rates of local recurrence, metastasis, and poor survival. Treatment of the primary tumor involves surgical excision with possible adjuvant radiation therapy, whereas regional nodal disease is treated with some combination of lymph node dissection and radiation therapy. Immune checkpoint inhibitors, such as avelumab and pembrolizumab, are first-line agents for metastatic MCC. Monitoring for recurrence can be aided by Merkel cell polyomavirus oncoprotein antibody titers.
Topics: Humans; Aged; Carcinoma, Merkel Cell; Skin Neoplasms; Lymph Node Excision; Merkel cell polyomavirus
PubMed: 36410971
DOI: 10.1016/j.det.2022.07.015 -
Clinical Transplantation Sep 2019The present AST-IDCOP guidelines update information on BK polyomavirus (BKPyV) infection, replication, and disease, which impact kidney transplantation (KT), but rarely...
The present AST-IDCOP guidelines update information on BK polyomavirus (BKPyV) infection, replication, and disease, which impact kidney transplantation (KT), but rarely non-kidney solid organ transplantation (SOT). As pretransplant risk factors in KT donors and recipients presently do not translate into clinically validated measures regarding organ allocation, antiviral prophylaxis, or screening, all KT recipients should be screened for BKPyV-DNAemia monthly until month 9, and then every 3 months until 2 years posttransplant. Extended screening after 2 years may be considered in pediatric KT. Stepwise immunosuppression reduction is recommended for KT patients with plasma BKPyV-DNAemia of >1000 copies/mL sustained for 3 weeks or increasing to >10 000 copies/mL reflecting probable and presumptive BKPyV-associated nephropathy, respectively. Reducing immunosuppression is also the primary intervention for biopsy-proven BKPyV-associated nephropathy. Hence, allograft biopsy is not required for treating BKPyV-DNAemic patients with baseline renal function. Despite virological rationales, proper randomized clinical trials are lacking to generally recommend treatment by switching from tacrolimus to cyclosporine-A, from mycophenolate to mTOR inhibitors or leflunomide or by the adjunct use of intravenous immunoglobulins, leflunomide, or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. Retransplantation after allograft loss due to BKPyV nephropathy can be successful if BKPyV-DNAemia is definitively cleared, independent of failed allograft nephrectomy.
Topics: Antiviral Agents; BK Virus; Humans; Organ Transplantation; Polyomavirus Infections; Practice Guidelines as Topic; Societies, Medical; Transplant Recipients; Tumor Virus Infections
PubMed: 30859620
DOI: 10.1111/ctr.13528 -
Journal of Neurovirology Oct 2023Since its definition 65 years ago, progressive multifocal leukoencephalopathy (PML) has continued to devastate a growing population of immunosuppressed patients despite... (Review)
Review
Since its definition 65 years ago, progressive multifocal leukoencephalopathy (PML) has continued to devastate a growing population of immunosuppressed patients despite major advances in our understanding of the causative JC virus (JCV). Unless contained by the immune system, JCV lyses host oligodendrocytes collateral to its life cycle, leading to demyelination, neurodegeneration, and death. Novel treatments have stagnated in the absence of an animal model while current antiviral agents fail to address the now ubiquitous polyomavirus. In this review, we highlight the established pathogenesis by which JCV infection progresses to PML, highlighting major challenges that must be overcome to eliminate the underlying virus and, therefore, the debilitating disease.
Topics: Animals; Humans; Leukoencephalopathy, Progressive Multifocal; JC Virus; Polyomavirus Infections; Immunocompromised Host
PubMed: 37659983
DOI: 10.1007/s13365-023-01164-w -
Der Pathologe Dec 2019Merkel-cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma named for its Merkel-cell-like ultrastructure. The neuroendocrine Merkel cell was... (Review)
Review
Merkel-cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma named for its Merkel-cell-like ultrastructure. The neuroendocrine Merkel cell was previously believed to be the cell of origin. However, Merkel cells are postmitotic and thus probably not the cell of origin of MCC. It is derived from an epidermal stem cell, which also might represent the cell of origin of MCC. Further putative cells of origin are dermal stem cells and pre/pro‑B cells, the latter showing some similar markers (e.g. PAX5).About 80% of MCCs are induced by the integration of DNA of the Merkel cell polyoma virus (MCPyV) into the genome. On the other hand, about 20% of MCCs show UV-induced mutations in numerous genes (e.g. TP53, RB1). In routine histology, MCC appears monomorphic and the diagnosis is confirmed by immunohistochemistry showing CK20 arranged in typical paranuclear plaques, together with the presence of neurofilaments and chromogranin A. Virus-positive and virus-negative MCC are not different histologically.UV-induced and viral neoantigens cause the strong immunogenicity of MCC. Moreover, over the last few years, the presence of PD-1 and PD-L1 has been demonstrated within tumor and immune cells. For the checkpoint inhibitors pembrolizumab and avelumab, responses of about 50% have been shown, independent of virus state. Circulating tumor cells (CTCs) seem to be helpful in tumor tracking. Further immunological and molecular studies are necessary for future individual therapies, also concerning immunocompromised patients.
Topics: Biomarkers, Tumor; Carcinoma, Merkel Cell; Humans; Immunohistochemistry; Merkel cell polyomavirus; Skin Neoplasms; Tumor Virus Infections
PubMed: 31820040
DOI: 10.1007/s00292-019-00705-7 -
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 -
Pediatric Nephrology (Berlin, Germany) Apr 2021After pediatric kidney transplantation, immunosuppressive therapy causes an increased risk of severe viral complications, especially from cytomegalovirus (CMV), BK... (Review)
Review
After pediatric kidney transplantation, immunosuppressive therapy causes an increased risk of severe viral complications, especially from cytomegalovirus (CMV), BK polyomavirus (BKPyV) or Epstein-Barr virus (EBV), and less frequent from adenovirus (ADV). However, suitable predictive markers for the individual outcome of viral infections are missing and the therapeutic management remains a challenge to the success of pediatric kidney transplantation. Virus-specific T cells are known for controlling viral replication and there is growing evidence that virus-specific T cells may serve as a prognostic marker to identify patients at risk for viral complications. This review provides an overview of the usability of virus-specific T cells for improving diagnostic and therapeutic management of viral infections with reference to the necessity of antiviral prophylaxis, timing of pre-emptive therapy, and dosing of immunosuppressive medication after pediatric kidney transplantation. Several studies demonstrated that high levels of virus-specific T cells are associated with decrease of virus load and favorable outcome, whereas lack of virus-specific T cells coincided with virus-induced complications. Accordingly, the additional monitoring of virus-specific T cells aims to personalize the management of antiviral therapy, identify overimmunosuppression, and avoid unnecessary therapeutic interventions. Prospective randomized trials in pediatric kidney recipients comparing standard antiviral and immunosuppressive regimens with T cell-guided therapeutic interventions are needed, before monitoring of virus-specific T cells is implemented in the routine care of pediatric kidney graft recipients.
Topics: Antiviral Agents; BK Virus; Child; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Kidney Transplantation; Polyomavirus Infections; Prospective Studies; T-Lymphocytes
PubMed: 32221706
DOI: 10.1007/s00467-020-04522-6