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American Journal of Transplantation :... May 2024The strategy for progressive multifocal leukoencephalopathy (PML) in solid organ transplant recipients primarily focuses on reducing immunosuppressive therapy. However,...
The strategy for progressive multifocal leukoencephalopathy (PML) in solid organ transplant recipients primarily focuses on reducing immunosuppressive therapy. However, this approach offers limited efficacy and carries a high risk of graft loss. Here, we present the case of a 64-year-old male kidney transplant recipient with a high degree of immunosuppression who developed PML in October 2022. Despite the standard reduction of immunosuppressive therapy, the patient's condition continued to deteriorate, as evidenced by worsening neurological symptoms and increasing JC virus (JCV) DNA levels in cerebrospinal fluid. This prompted the innovative use of BKPyV-virus-specific T cell (BKPyV-VST) therapy, given the genetic similarities between BK and JCVs. Infusion of third-party donor BKPyV-VST resulted in clinical stabilization, a significant reduction in JCV-DNA levels, and the emergence of a JCV-specific T cell response, as observed in enzyme-linked immunospot assays and TCRβ sequencing. This represents the first case report of successful third-party BKPyV-VST therapy in a kidney recipient presenting PML, without graft-versus-host disease or graft dysfunction.
PubMed: 38734417
DOI: 10.1016/j.ajt.2024.05.003 -
BMJ Case Reports Apr 2024A middle-aged man with progressive multifocal leukoencephalopathy (PML) in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier on haemodialysis presented with mild...
A middle-aged man with progressive multifocal leukoencephalopathy (PML) in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier on haemodialysis presented with mild dysarthria and ataxia. Brain MRI revealed asymmetric T-hyperintense lesions in the cerebral white matter, cerebellum and brainstem. A small amount of JC virus (JCV) genome in cerebrospinal fluid was detected by PCR and cerebellar biopsy demonstrated JCV-DNA presence. Pathological findings showed demyelinating lesions and glial cells with mildly enlarged nuclei, accompanied by T-lymphocytes, neutrophils and plasma cell infiltration. The CD4+/CD8+ratio was 0.83. High-dose corticosteroid therapy was effective for inflammatory PML lesions, and the administration of mefloquine combined with mirtazapine led to favourable outcome. The encephalitis in this case is considered to have occurred secondarily to JCV infection in the presence of HTLV-1 infection. Therefore, it is crucial to investigate the presence of HTLV-1 in order to understand the aetiology of this brain inflammation.
Topics: Humans; Leukoencephalopathy, Progressive Multifocal; Male; HTLV-I Infections; Middle Aged; Human T-lymphotropic virus 1; JC Virus; Coinfection; Mirtazapine; Magnetic Resonance Imaging; Mefloquine
PubMed: 38688573
DOI: 10.1136/bcr-2023-257805 -
International Journal of Molecular... Apr 2024CX3CL1, also named fractalkine or neurotactin, is the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both... (Review)
Review
CX3CL1, also named fractalkine or neurotactin, is the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both membrane-anchored and soluble forms, with each mediating distinct biological activities. CX3CL1 signals are transmitted through its unique receptor, CX3CR1, primarily expressed in the microglia of the central nervous system (CNS). In the CNS, CX3CL1 acts as a regulator of microglia activation in response to brain disorders or inflammation. Recently, there has been a growing interest in the role of CX3CL1 in regulating cell adhesion, chemotaxis, and host immune response in viral infection. Here, we provide a comprehensive review of the changes and function of CX3CL1 in various viral infections, such as human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus, and cytomegalovirus (CMV) infection, to highlight the emerging roles of CX3CL1 in viral infection and associated diseases.
Topics: Chemokine CX3CL1; Humans; Virus Diseases; Animals; COVID-19; SARS-CoV-2; Microglia; CX3C Chemokine Receptor 1
PubMed: 38674036
DOI: 10.3390/ijms25084451 -
Journal of Clinical Medicine Apr 2024The John Cunningham virus (JCV) is a polyomavirus that usually infects people at a young age and does not cause any symptoms in immunocompetent individuals. However, in... (Review)
Review
The John Cunningham virus (JCV) is a polyomavirus that usually infects people at a young age and does not cause any symptoms in immunocompetent individuals. However, in immunocompromised individuals, such as kidney transplant recipients, JCV can cause severe and potentially fatal disease. Unfortunately, JCV has not been researched as extensively as the BK virus and is not mentioned in relevant kidney transplant guidelines. This lack of attention to JCV can lead to less consideration in kidney transplant patients' care. Surveillance using locally available diagnostic methods is of the utmost importance. The presence of JCV can be diagnosed with urine decoy cells, viruria, or viremia verified by the PCR method. A low threshold for considering JCV as a possible cause of any neurological or renal dysfunction in kidney transplant recipients must be maintained. In such cases, kidney and brain biopsy are indicated. Maintaining the appropriate immunosuppression while avoiding over-immunosuppression to prevent JCV disease is crucial, and the approach should be individual, according to overall immunological risk. We hypothesize that the presence of the JCV can indicate overt immunosuppression and identify kidney transplant recipients more prone to opportunistic infections and diseases, including some malignancies. To explore that, future observational studies are needed.
PubMed: 38673491
DOI: 10.3390/jcm13082217 -
Health Science Reports Apr 2024Gastric cancer is a significant global issue with a high death rate. This malignancy could be associated with several viral agents such as EBV, CMV, HHV-6, JCV, and BKV.
Investigation of Epstein-Barr virus, Cytomegalovirus, Human herpesvirus 6, and Polyoma viruses (JC virus, BK virus) among Gastric cancer patients: A cross sectional study.
BACKGROUND AND AIMS
Gastric cancer is a significant global issue with a high death rate. This malignancy could be associated with several viral agents such as EBV, CMV, HHV-6, JCV, and BKV.
OBJECTIVE
Evaluation of EBV, CMV, HHV-6 ,and JCV, BKV frequency among gastric cancer patients.
METHODS
In this cross-sectional study, a total number of 60 gastric cancer specimens (32 male, 28 female) were retrieved from the pathology lab. Formalin-fixed paraffin-embedded tissue was used for molecular testing. DNA was extracted from samples, according to protocol, and used for PCR reaction. Polymerase chain reactions were used to assess CMV, EBV, HHV-6, JCV, and BKV frequency.
RESULTS AND CONCLUSION
The mean age of the participants was 61 years and 53.3% (32) of the participants were Male. A total number of 5 samples (8.34%) were infected with viral agents. Four male gastric samples were infected with EBV (6.67%) and only one female sample contained the BKV genome (1.67%). Totally 8.34% of the samples were infected with EBV and BKV. The CMV, HHV-6, and JCV genome was not detected in the samples. In conclusion, the presence of two viral agents including EBV and BKV among male and female samples respectively, and the genome of other viruses were not detected.
PubMed: 38650724
DOI: 10.1002/hsr2.2043 -
The Lancet. Neurology May 2024Progressive multifocal leukoencephalopathy is a rare but devastating demyelinating disease caused by the JC virus (JCV), for which no therapeutics are approved. To make... (Review)
Review
Progressive multifocal leukoencephalopathy is a rare but devastating demyelinating disease caused by the JC virus (JCV), for which no therapeutics are approved. To make progress towards addressing this unmet medical need, innovations in clinical trial design are needed. Quantitative JCV DNA in CSF has the potential to serve as a valuable biomarker of progressive multifocal leukoencephalopathy disease and treatment response in clinical trials to expedite therapeutic development, as do neuroimaging and other fluid biomarkers such as neurofilament light chain. Specifically, JCV DNA in CSF could be used in clinical trials as an entry criterion, stratification factor, or predictor of clinical outcomes. Insights from the investigation of candidate biomarkers for progressive multifocal leukoencephalopathy might inform approaches to biomarker development for other rare diseases.
Topics: Humans; Biomarkers; DNA Copy Number Variations; DNA, Viral; JC Virus; Leukoencephalopathy, Progressive Multifocal; Clinical Trials as Topic
PubMed: 38631769
DOI: 10.1016/S1474-4422(24)00099-1 -
The Lancet. Neurology May 2024
Topics: Humans; Leukoencephalopathy, Progressive Multifocal; Magnetic Resonance Imaging; Biomarkers; JC Virus
PubMed: 38631756
DOI: 10.1016/S1474-4422(24)00132-7 -
BMC Urology Apr 2024JC polyomavirus (JCPyV) is a human polyomavirus that can establish lifelong persistent infection in the majority of adults. It is typically asymptomatic in...
JC polyomavirus (JCPyV) is a human polyomavirus that can establish lifelong persistent infection in the majority of adults. It is typically asymptomatic in immunocompetent individuals. However, there is a risk of developing progressive multifocal leukoencephalopathy (PML) in immunocompromised or immunosuppressed patients. Though JCPyV commonly resides in the kidney-urinary tract, its involvement in urinary system diseases is extremely rare. Here, we reported a case of a 60-year-old male patient with coronavirus disease 2019 (COVID-19) infection who developed hemorrhagic cystitis after receiving treatment with nirmatrelvir 300 mg/ritonavir 100 mg quaque die (QD). Subsequent metagenomic next-generation sequencing (mNGS) confirmed the infection to be caused by JCPyV type 2. Then, human immunoglobulin (PH4) for intravenous injection at a dose of 25 g QD was administered to the patient. Three days later, the hematuria resolved. This case illustrates that in the setting of compromised host immune function, JCPyV is not limited to causing central nervous system diseases but can also exhibit pathogenicity in the urinary system. Moreover, mNGS technology facilitates rapid diagnosis of infectious etiology by clinical practitioners, contributing to precise treatment for patients.
Topics: Humans; Male; Middle Aged; COVID-19; Cystitis, Hemorrhagic; JC Virus; Leukoencephalopathy, Progressive Multifocal; Polyomavirus Infections
PubMed: 38627797
DOI: 10.1186/s12894-024-01464-1 -
BioRxiv : the Preprint Server For... Apr 2024Ebola virus (EBOV) is a high-consequence filovirus that gives rise to frequent epidemics with high case fatality rates and few therapeutic options. Here, we applied...
Ebola virus (EBOV) is a high-consequence filovirus that gives rise to frequent epidemics with high case fatality rates and few therapeutic options. Here, we applied image-based screening of a genome-wide CRISPR library to systematically identify host cell regulators of Ebola virus infection in 39,085,093 million single cells. Measuring viral RNA and protein levels together with their localization in cells identified over 998 related host factors and provided detailed information about the role of each gene across the virus replication cycle. We trained a deep learning model on single-cell images to associate each host factor with predicted replication steps, and confirmed the predicted relationship for select host factors. Among the findings, we showed that the mitochondrial complex III subunit UQCRB is a post-entry regulator of Ebola virus RNA replication, and demonstrated that UQCRB inhibition with a small molecule reduced overall Ebola virus infection with an IC50 of 5 μM. Using a random forest model, we also identified perturbations that reduced infection by disrupting the equilibrium between viral RNA and protein. One such protein, STRAP, is a spliceosome-associated factor that was found to be closely associated with VP35, a viral protein required for RNA processing. Loss of STRAP expression resulted in a reduction in full-length viral genome production and subsequent production of non-infectious virus particles. Overall, the data produced in this genome-wide high-content single-cell screen and secondary screens in additional cell lines and related filoviruses (MARV and SUDV) revealed new insights about the role of host factors in virus replication and potential new targets for therapeutic intervention.
PubMed: 38617272
DOI: 10.1101/2024.04.06.588168 -
Nature Communications Apr 2024Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory... (Randomized Controlled Trial)
Randomized Controlled Trial
Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent influenza vaccination in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic (pH1N1) and monitored for infection. We found that seasonal vaccination increases pH1N1 specific antibodies and FcR effector functions. Furthermore, prospective baseline antibody profiles after seasonal vaccination, prior to pH1N1 infection, show that unvaccinated uninfected children have elevated ADCC effector function, FcγR3a and FcγR2a binding antibodies to multiple pH1N1 proteins, past seasonal and avian (H5, H7 and H9) strains. Whereas, children that became pH1N1 infected after seasonal vaccination have antibodies focussed to seasonal strains without FcR functions, and greater aggregated HA-specific profiles for IgM and IgG3. Modeling to predict infection susceptibility, ranked baseline hemagglutination antibody inhibition as the highest contributor to lack of pH1N1 infection, in combination with features that include pH1-IgG1, H1-stem responses and FcR binding to seasonal vaccine and pH1 proteins. Thus, seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive antibodies with Fc potential without vaccination and may be considered 'elite influenza controllers'.
Topics: Child; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Prospective Studies; Antibodies, Viral; Antibodies, Neutralizing; Immunoglobulin G; Influenza Vaccines
PubMed: 38615070
DOI: 10.1038/s41467-024-47590-0