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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 -
Current Opinion in Virology Apr 2021Polyomaviruses are mostly non-pathogenic, yet some can cause human disease especially under conditions of immunosuppression, including JC, BK, and Merkel cell... (Review)
Review
Polyomaviruses are mostly non-pathogenic, yet some can cause human disease especially under conditions of immunosuppression, including JC, BK, and Merkel cell polyomaviruses. Direct interactions between viruses and the host early during infection dictate the outcome of disease, many of which remain enigmatic. However, significant work in recent years has contributed to our understanding of how this virus family establishes an infection, largely due to advances made for animal polyomaviruses murine and SV40. Here we summarize the major findings that have contributed to our understanding of polyomavirus entry, trafficking, disassembly, signaling, and immune evasion during the infectious process and highlight major unknowns in these processes that are open areas of study.
Topics: Animals; Cell Nucleus; Endoplasmic Reticulum; Endosomes; Humans; Immune Evasion; Polyomavirus; Signal Transduction; Virus Attachment; Virus Internalization
PubMed: 33690104
DOI: 10.1016/j.coviro.2021.02.004 -
Infectious Disease Clinics of North... Jun 2020The risk of JC polyomavirus encephalopathy varies among biologic classes and among agents within the same class. Of currently used biologics, the highest risk is seen... (Review)
Review
The risk of JC polyomavirus encephalopathy varies among biologic classes and among agents within the same class. Of currently used biologics, the highest risk is seen with natalizumab followed by rituximab. Multiple other agents have also been implicated. Drug-specific causality is difficult to establish because many patients receive multiple immunomodulatory medications concomitantly or sequentially, and have other immunocompromising factors related to their underlying disease. As use of biologic therapies continues to expand, further research is needed into pathogenesis, treatment, and prevention of JC polyomavirus encephalopathy such that risk for its development is better understood and mitigated, if not eliminated altogether.
Topics: Biological Products; Comorbidity; Humans; Immunity, Humoral; JC Virus; Leukoencephalopathy, Progressive Multifocal; Polyomavirus Infections; Prognosis; Risk Factors; Virus Activation; Virus Latency
PubMed: 32444013
DOI: 10.1016/j.idc.2020.02.007 -
Journal of Medical Virology Sep 2023Bladder cancer (BC) is a complex disease affecting the urinary system and is regulated by several carcinogenic factors. Viral infection is one such factor that has... (Review)
Review
Bladder cancer (BC) is a complex disease affecting the urinary system and is regulated by several carcinogenic factors. Viral infection is one such factor that has attracted extensive attention in BC. Human papillomavirus (HPV) is the most common sexually transmitted infection, and although multiple researchers have explored the role of HPV in BC, a consensus has not yet been reached. In addition, HPV-associated viruses (e.g., human immunodeficiency virus, herpes simplex virus, BK virus, and JC virus) appear to be responsible for the occurrence and progression of BC. This study systematically reviews the relationship between HPV-associated viruses and BC to elucidate the role of these viruses in the onset and progression of BC. In addition, the study aims to provide a greater insight into the biology of HPV-associated viruses, and assess potential strategies for treating virus-induced BC. The study additionally focuses on the rapid development of oncolytic viruses that provide a potentially novel option for the treatment of BC.
Topics: Humans; Human Papillomavirus Viruses; Satellite Viruses; Papillomavirus Infections; Urinary Bladder Neoplasms; BK Virus
PubMed: 37706751
DOI: 10.1002/jmv.29088 -
Journal of Neurology May 2022Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral disease of the brain-caused by human polyomavirus 2. It affects patients whose immune system... (Review)
Review
Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral disease of the brain-caused by human polyomavirus 2. It affects patients whose immune system is compromised by a corresponding underlying disease or by drugs. Patients with an underlying lymphoproliferative disease have the worst prognosis with a mortality rate of up to 90%. Several therapeutic strategies have been proposed but failed to show any benefit so far. Therefore, the primary therapeutic strategy aims to reconstitute the impaired immune system to generate an effective endogenous antiviral response. Recently, anti-PD-1 antibodies and application of allogeneic virus-specific T cells demonstrated promising effects on the outcome in individual PML patients. This article aims to provide a detailed overview of the literature with a focus on these two treatment approaches.
Topics: Brain; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Prognosis
PubMed: 34994851
DOI: 10.1007/s00415-021-10952-5 -
Microbial Pathogenesis Dec 2022The aim of this study was to investigate the prevalence and potential association between the infection with some members of the polyomaviridae family of viruses and... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this study was to investigate the prevalence and potential association between the infection with some members of the polyomaviridae family of viruses and development of the brain tumors.
METHODS
A systematic literature search was performed by finding relevant cross-sectional and case-control studies from a large online database. Heterogeneity, OR, and corresponding 95% CI were applied to all studies by meta-analysis and forest plots. The analysis was performed using Stata Software v.14.
RESULTS
Twenty-three articles (33 datasets) were included in the meta-analysis, four (four datasets) of which were case/control studies and the rest were cross-sectional. The pooled prevalence of polyomaviruses among brain cancer patients was 13% (95% CI: 8-20%; I = 96.91%). In subgroup analysis, the pooled prevalence of JCV, SV40, BKV and Merkel cell polyomavirus was 20%, 8%, 6%, and 16%, respectively. An association was found between polyomavirus infection and brain cancer [summary OR 7.22 (95% CI (2.36-22.05); I = 0%)]. The subgroup analysis, based on the virus type, demonstrated a strong association between JCV infection and brain cancer development [summary OR 10.34 (95% CI 1.10-97.42; I = 0%)].
CONCLUSION
The present study showed a significant association between polyomavirus infection and brain tumors. Moreover, these results suggest that polyomavirus infection may be a potential risk factor for the development of brain cancer.
Topics: Humans; Polyomavirus Infections; Polyomavirus; Brain Neoplasms; Case-Control Studies; JC Virus
PubMed: 36183958
DOI: 10.1016/j.micpath.2022.105797 -
Revista Da Sociedade Brasileira de... 2020Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by reactivation of JC virus (JCV).
INTRODUCTION
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by reactivation of JC virus (JCV).
METHODS
We described the profile of laboratory-confirmed PML cases among AIDS patients.
RESULTS
A total of 43 HIV patients with clinical conditions compatible with PML were obtained; 5 cases were confirmed by JCV testing. The main clinical finding was mental confusion. Median CD4 count was 54 cells/mm³.
CONCLUSIONS
Three of the five confirmed PML cases died; the time between diagnosis and death was 2, 5, and 6 months. It is important to consider JCV infection as a differential diagnosis.
Topics: Acquired Immunodeficiency Syndrome; CD4 Lymphocyte Count; DNA, Viral; HIV Infections; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal
PubMed: 33338109
DOI: 10.1590/0037-8682-0252-2020 -
Experimental Neurology Jul 2023Microphysiological systems (MPS) are 2D or 3D multicellular constructs able to mimic tissue microenvironments. The latest models encompass a range of techniques,... (Review)
Review
Microphysiological systems (MPS) are 2D or 3D multicellular constructs able to mimic tissue microenvironments. The latest models encompass a range of techniques, including co-culturing of various cell types, utilization of scaffolds and extracellular matrix materials, perfusion systems, 3D culture methods, 3D bioprinting, organ-on-a-chip technology, and examination of tissue structures. Several human brain 3D cultures or brain MPS (BMPS) have emerged in the last decade. These organoids or spheroids are 3D culture systems derived from induced pluripotent cells or embryonic stem cells that contain neuronal and glial populations and recapitulate structural and physiological aspects of the human brain. BMPS have been introduced recently in the study and modeling of neuroinfectious diseases and have proven to be useful in establishing neurotropism of viral infections, cell-pathogen interactions needed for infection, assessing cytopathological effects, genomic and proteomic profiles, and screening therapeutic compounds. Here we review the different methodologies of organoids used in neuroinfectious diseases including spheroids, guided and unguided protocols as well as microglia and blood-brain barrier containing models, their specific applications, and limitations. The review provides an overview of the models existing for specific infections including Zika, Dengue, JC virus, Japanese encephalitis, measles, herpes, SARS-CoV2, and influenza viruses among others, and provide useful concepts in the modeling of disease and antiviral agent screening.
Topics: Humans; Microphysiological Systems; Proteomics; RNA, Viral; COVID-19; SARS-CoV-2; Brain; Zika Virus; Zika Virus Infection; Induced Pluripotent Stem Cells
PubMed: 37061175
DOI: 10.1016/j.expneurol.2023.114409 -
International Journal of Molecular... Feb 2022CRISPR/Cas9 provides a robust and widely adaptable system with enormous potential for genome editing directed towards generating useful products. It has been used... (Review)
Review
CRISPR/Cas9 provides a robust and widely adaptable system with enormous potential for genome editing directed towards generating useful products. It has been used extensively to generate resistance against viruses infecting plants with more effective and prolonged efficiency as compared with previous antiviral approaches, thus holding promise to alleviate crop losses. In this review, we have discussed the reports of CRISPR/Cas-based virus resistance strategies against plant viruses. These strategies include approaches targeting single or multiple genes (or non-coding region) in the viral genome and targeting host factors essential for virus propagation. In addition, the utilization of base editing has been discussed to generate transgene-free plants resistant to viruses. This review also compares the efficiencies of these approaches. Finally, we discuss combinatorial approaches, including multiplexing, to increase editing efficiency and bypass the generation of escape mutants.
Topics: CRISPR-Cas Systems; Gene Editing; Genome, Plant; Genome, Viral; Plant Viruses; Plants, Genetically Modified
PubMed: 35216418
DOI: 10.3390/ijms23042303 -
Viruses Nov 2022The organization and dynamics of plasma membrane receptors are a critical link in virus-receptor interactions, which finetune signaling efficiency and determine cellular...
The organization and dynamics of plasma membrane receptors are a critical link in virus-receptor interactions, which finetune signaling efficiency and determine cellular responses during infection. Characterizing the mechanisms responsible for the active rearrangement and clustering of receptors may aid in developing novel strategies for the therapeutic treatment of viruses. Virus-receptor interactions are poorly understood at the nanoscale, yet they present an attractive target for the design of drugs and for the illumination of viral infection and pathogenesis. This study utilizes super-resolution microscopy and related techniques, which surpass traditional microscopy resolution limitations, to provide both a spatial and temporal assessment of the interactions of human JC polyomavirus (JCPyV) with 5-hydroxytrypamine 2 receptors (5-HTRs) subtypes during viral entry. JCPyV causes asymptomatic kidney infection in the majority of the population and can cause fatal brain disease, and progressive multifocal leukoencephalopathy (PML), in immunocompromised individuals. Using Fluorescence Photoactivation Localization Microscopy (FPALM), the colocalization of JCPyV with 5-HT receptor subtypes (5-HT, 5-HT, and 5-HT) during viral attachment and viral entry was analyzed. JCPyV was found to significantly enhance the clustering of 5-HT receptors during entry. Cluster analysis of infected cells reveals changes in 5-HT receptor cluster attributes, and radial distribution function (RDF) analyses suggest a significant increase in the aggregation of JCPyV particles colocalized with 5-HT receptor clusters in JCPyV-infected samples. These findings provide novel insights into receptor patterning during viral entry and highlight improved technologies for the future development of therapies for JCPyV infection as well as therapies for diseases involving 5-HT receptors.
Topics: Humans; JC Virus; Serotonin; Leukoencephalopathy, Progressive Multifocal; Polyomavirus Infections; Virus Attachment
PubMed: 36560603
DOI: 10.3390/v14122597