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European Journal of Neurology Mar 2021Progressive multifocal leukoencephalopathy (PML) is a severe infection caused by the polyomavirus JC that develops in the central nervous system (CNS) of...
BACKGROUND AND PURPOSE
Progressive multifocal leukoencephalopathy (PML) is a severe infection caused by the polyomavirus JC that develops in the central nervous system (CNS) of immunosuppressed patients. The infection frequently starts in the brain hemispheres and can spread into other CNS regions such as the brainstem. Initial isolated PML brainstem lesions are exceptional. We aimed to describe the challenging diagnosis of PML with isolated brainstem lesions at the time of disease onset.
METHODS
We describe a case of PML starting with an isolated brainstem lesion and reviewed clinical, radiological, and biological features of all the reported cases of isolated brainstem PML.
RESULTS
Isolated brainstem PML at disease onset is extremely rare. In addition to our case, only nine PML cases presenting with strictly isolated radioanatomical brainstem location at the time of disease onset were retrieved through the literature. All patients share similar brain magnetic resonance imaging features, without contrast enhancement. Eight patients presented with initial clinical worsening, but full recovery occurred in three patients, partial recovery in two, and death in three. Even if prognosis is reserved because of the surrounding vital structures in the brainstem, clinical recovery may occur.
CONCLUSIONS
This case report and literature review emphasize that isolated brainstem lesion is an atypical presentation of PML at disease onset.
Topics: Brain; Brain Stem; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Magnetic Resonance Imaging; Male; Middle Aged
PubMed: 33128290
DOI: 10.1111/ene.14617 -
Food and Environmental Virology Sep 2021Water and wastewater virological quality is a significant public health issue. Viral agents include emerging and re-emerging pathogens characterized by extremely small... (Review)
Review
Water and wastewater virological quality is a significant public health issue. Viral agents include emerging and re-emerging pathogens characterized by extremely small size, and high environmental stability. Since the mainly used conventional disinfection methods are usually not able to achieve complete disinfection of viral and other microbial targets, in real water and wastewater matrices, effective strategies for the treatment, use and reuse of water and the development of next-generation water supply systems are required. The scope of the present systematic review was to summarize research data on the application of advanced oxidation processes (AOPs) for viral disinfection of water and wastewater. A literature survey was conducted using the electronic databases PubMed, Scopus, and Web of Science. This comprehensive research yielded 23 records which met the criteria and were included and discussed in this review. Most of the studies (14/23) used only MS2 bacteriophage as an index virus, while the remaining studies (9/23) used two or more viral targets, including phages (MS2, T4, T7, phiX174, PRD-1, S2, ϕB124-14, ϕcrAssphage) and/or Adenovirus, Aichivirus, Norovirus (I, II, IV), Polyomavirus (JC and BK), Sapovirus, Enterovirus, Coxsackievirus B3, Echovirus, and Pepper mild mottle virus. The vast majority of the studies applied a combination of two or more treatments and the most frequently used process was ultraviolet light-hydrogen peroxide (UV/HO) advanced oxidation. The review is expected to highlight the potential of the AOPs for public health protection from the waterborne viral exposure.
Topics: Disinfection; Hydrogen Peroxide; Ultraviolet Rays; Wastewater; Water; Water Purification
PubMed: 34125359
DOI: 10.1007/s12560-021-09481-1 -
The European Respiratory Journal Sep 2020https://bit.ly/3fqkiyp
https://bit.ly/3fqkiyp
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Disease Outbreaks; Gross Domestic Product; Health Expenditures; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Linear Models; Pandemics; Pneumonia, Viral; Population Density; Regression Analysis; Risk Factors; SARS-CoV-2; Socioeconomic Factors; Urbanization
PubMed: 32675209
DOI: 10.1183/13993003.01400-2020 -
NPJ Digital Medicine Apr 2022As clinicians and scientists gather more data on the clinical trajectory of COVID-19 and the biology of its causative agent, the SARS-CoV-2 virus, novel strategies are...
As clinicians and scientists gather more data on the clinical trajectory of COVID-19 and the biology of its causative agent, the SARS-CoV-2 virus, novel strategies are needed to integrate these data to inform new therapies. A recent study by Howell et al. introduces a network model of viral-host interactions to produce explainable and testable predictions for treatment effects. Their model was consistent with experimental data and recommended treatments, and one of its predicted drug combinations was validated through in vitro assays. These findings support the utility of computational strategies for leveraging the vast literature on COVID-19 to generate insights for drug repurposing.
PubMed: 35459899
DOI: 10.1038/s41746-022-00599-5 -
American Journal of Transplantation :... Sep 2019Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus...
Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.
Topics: Adult; BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Female; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Polyomavirus Infections; Premedication; Proportional Hazards Models; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Tumor Virus Infections; Valacyclovir; Valganciclovir; Viremia
PubMed: 31220412
DOI: 10.1111/ajt.15507 -
Frontiers in Microbiology 2022Early growth response 1 (EGR1) is a multifunctional mammalian transcription factor capable of both enhancing and/or inhibiting gene expression. EGR1 can be activated by... (Review)
Review
Early growth response 1 (EGR1) is a multifunctional mammalian transcription factor capable of both enhancing and/or inhibiting gene expression. EGR1 can be activated by a wide array of stimuli such as exposure to growth factors, cytokines, apoptosis, and various cellular stress states including viral infections by both DNA and RNA viruses. Following induction, EGR1 functions as a convergence point for numerous specialized signaling cascades and couples short-term extracellular signals to influence transcriptional regulation of genes required to initiate the appropriate biological response. The role of EGR1 has been extensively studied in both physiological and pathological conditions of the adult nervous system where it is readily expressed in various regions of the brain and is critical for neuronal plasticity and the formation of memories. In addition to its involvement in neuropsychiatric disorders, EGR1 has also been widely examined in the field of cancer where it plays paradoxical roles as a tumor suppressor gene or oncogene. EGR1 is also associated with multiple viral infections such as Venezuelan equine encephalitis virus (VEEV), Kaposi's sarcoma-associated herpesvirus (KSHV), herpes simplex virus 1 (HSV-1), human polyomavirus JC virus (JCV), human immunodeficiency virus (HIV), and Epstein-Barr virus (EBV). In this review, we examine EGR1 and its role(s) during viral infections. First, we provide an overview of EGR1 in terms of its structure, other family members, and a brief overview of its roles in non-viral disease states. We also review upstream regulators of EGR1 and downstream factors impacted by EGR1. Then, we extensively examine EGR1 and its roles, both direct and indirect, in regulating replication of DNA and RNA viruses.
PubMed: 36338037
DOI: 10.3389/fmicb.2022.1020220 -
Viruses Oct 2020Polyomaviruses are ubiquitous human pathogens that cause lifelong, asymptomatic infections in healthy individuals. Although these viruses are restrained by an intact... (Review)
Review
Polyomaviruses are ubiquitous human pathogens that cause lifelong, asymptomatic infections in healthy individuals. Although these viruses are restrained by an intact immune system, immunocompromised individuals are at risk for developing severe diseases driven by resurgent viral replication. In particular, loss of immune control over JC polyomavirus can lead to the development of the demyelinating brain disease progressive multifocal leukoencephalopathy (PML). Viral isolates from PML patients frequently carry point mutations in the major capsid protein, VP1, which mediates virion binding to cellular glycan receptors. Because polyomaviruses are non-enveloped, VP1 is also the target of the host's neutralizing antibody response. Thus, VP1 mutations could affect tropism and/or recognition by polyomavirus-specific antibodies. How these mutations predispose susceptible individuals to PML and other JCPyV-associated CNS diseases remains to be fully elucidated. Here, we review the current understanding of polyomavirus capsid mutations and their effects on viral tropism, immune evasion, and virulence.
Topics: Animals; Capsid; Capsid Proteins; Host Specificity; Humans; Immune Evasion; JC Virus; Leukoencephalopathy, Progressive Multifocal; Mice; Mutation; Viral Tropism; Virus Replication
PubMed: 33053912
DOI: 10.3390/v12101156 -
Brain : a Journal of Neurology Apr 2022Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the CNS caused by the JC virus, which infects white and grey matter cells and leads to... (Review)
Review
Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the CNS caused by the JC virus, which infects white and grey matter cells and leads to irreversible demyelination and neuroaxonal damage. Brain MRI, in addition to the clinical presentation and demonstration of JC virus DNA either in the CSF or by histopathology, is an important tool in the detection of PML. In clinical practice, standard MRI pulse sequences are utilized for screening, diagnosis and monitoring of PML, but validated imaging-based outcome measures for use in prospective, interventional clinical trials for PML have yet to be established. We review the existing literature regarding the use of MRI and PET in PML and discuss the implications of PML histopathology for neuroradiology. MRI not only demonstrates the localization and extent of PML lesions, but also mirrors the tissue destruction, ongoing viral spread, and resulting inflammation. Finally, we explore the potential for imaging measures to serve as an outcome in PML clinical trials and provide recommendations for current and future imaging outcome measure development in this area.
Topics: Brain; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Magnetic Resonance Imaging; Prospective Studies
PubMed: 34791056
DOI: 10.1093/brain/awab419 -
The FEBS Journal Oct 2022JC polyomavirus (JCPyV), a ubiquitous human pathogen, causes several devastating brain diseases in immune-compromised individuals. The most notable of these... (Review)
Review
JC polyomavirus (JCPyV), a ubiquitous human pathogen, causes several devastating brain diseases in immune-compromised individuals. The most notable of these JCPyV-associated CNS diseases is the frequently fatal demyelinating brain disease progressive multifocal leukoencephalopathy (PML). PML, an AIDS-defining disease in the pre-cART epoch, has emerged as a life-threatening complication in patients receiving immunomodulatory agents for autoimmune and inflammatory disorders and treatment for certain hematological malignancies. Among the rapidly expanding list of PML-associated biologics, natalizumab (Tysabri®) has the highest incidence and is an ominous sequela for multiple sclerosis (MS) patients who otherwise benefit from dramatic reductions in relapses using this immunomodulatory agent. Drug withdrawal, the only therapeutic option for PML, is often complicated by a high-mortality cerebral inflammatory reaction. No anti-JCPyV agents are available. Lack of a tractable animal model of polyomavirus-induced central nervous system (CNS) disease is an acknowledged bottleneck to elucidating PML pathogenesis, immunological mechanisms that control JCPyV, in vivo evaluation of agents that inhibit polyomavirus replication in tissue culture, and uncovering early events that presage JCPyV-associated neuropathology. The natural virus-host mouse polyomavirus (MuPyV) model has recently been developed to explore mechanisms of polyomavirus-associated CNS disease. In this review, we will cover the benefits of using the MuPyV model to answer fundamental questions about innate and adaptive immune control of JCPyV, the impact of immunomodulation on JCPyV pathogenesis, and how this MuPyV CNS infection model will help improve criteria for identifying patients at risk for JCPyV-associated CNS diseases before the development of irreversible lesions.
Topics: Animals; Biological Products; Disease Models, Animal; Humans; Immunomodulating Agents; JC Virus; Leukoencephalopathy, Progressive Multifocal; Mice; Natalizumab; Polyomavirus
PubMed: 34145975
DOI: 10.1111/febs.16083 -
IScience Dec 2023Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To...
Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence employing single-cell protein and transcriptional profiling complemented with matched serum proteomics and metabolomics as well as multi-omics analysis. At the acute time point, we detected both elevation of pro-inflammatory markers in innate immune cell types and reduction of regulatory T cell activity in participants with severe infection, whereas asymptomatic donors had higher expression of genes associated with anti-inflammatory CD16 monocytes. Therefore, we demonstrated the potential of systems immunology using multiple cell-type and cell-state-specific analyses to identify correlates of infection severity and host cellular activity contributing to an effective anti-viral response.
PubMed: 38047068
DOI: 10.1016/j.isci.2023.108387