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Серотониновый рецептор 2А блокировщик (рисперидон) не оказывает воздействия на полиомавирусную инфекцию основных клеток плода человека.

В одном из недавних докладов было показано, что для заражения глиальных клеток вирус JC (JCV) использует рецептор серотонина 2A (5HT(2A)R). Для оценки способности мощного блокирующего устройства 5HT(2A)R, ризперидона, ингибировать заражение JCV, авторы лечили первичные клетки плода (PHFG) в vitro ризперидоном в течение 24 часов и вакцинировали его JCV(Mad1). Не было никаких существенных различий в копиях генома JCV или расшифровках mRNA и белковом выражении в лечебных и ризперидоновых клетках, обработанных PHFG. Эти данные свидетельствуют о том, что ризперидон не препятствует вложению, интерна

Совпадение в аннотации оригинала
A recent report demonstrated that JC virus (JCV) employs serotonin receptor 2A (5HT(2A)R) to infect the glial cells. To assess the ability of a potent 5HT(2A)R blocker, risperidone, to inhibit JCV infection, the authors treated primary human fetal glial (PHFG) cells in vitro with risperidone for 24 h and inoculated with JCV(Mad1). There was no significant di…

Successful treatment of severe, refractory polyomavirus disease with partially HLA-matched donor-derived BKPyV-specific T cells in a pediatric kidney recipient.

BK polyomavirus-associated nephropathy is a significant therapeutic challenge in kidney transplant recipients, often leading to allograft dysfunction. We report on a 12-year-old male kidney transplant recipient with severe, biopsy-proven BK polyomavirus-associated nephropathy and concurrent JC polyomavirus (JCPyV)-associated neurological symptoms. Due to failure of standard therapy, adoptive transfer of partially HLA-matched, BK polyomavirus-specific T cells from the kidney donor was administered as rescue therapy. The intervention induced a rapid decline in both BK polyomavirus (BKPyV) and JC

Viral miRNAs in plasma and urine divulge JC polyomavirus infection.

BACKGROUND: JC polyomavirus (JCPyV) is a widespread human polyomavirus that usually resides latently in its host, but can be reactivated under immune-compromised conditions potentially causing Progressive Multifocal Leukoencephalopathy (PML). JCPyV encodes its own microRNA, jcv-miR-J1. METHODS: We have investigated in 50 healthy subjects whether jcv-miR-J1-5p (and its variant jcv-miR-J1a-5p) can be detected in plasma or urine. RESULTS: We found that the overall detection rate of JCPyV miRNA was 74% (37/50) in plasma and 62% (31/50) in urine. Subjects were further categorized based on JCPyV V

Update on disease-modifying therapies for multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system (CNS). It predominantly affects young women an … ion. However, the high risk of progressive multifocal leukoencephalopathy (PML), which is caused by JC virus infection in the brain, tempers the more widespread use of this agent; nevertheless, JC virus antibody tests have helped to stratify the risk of PML. Alemtuzumab, which also has a considerable side effect profile, is likewise highly efficacious. Ocr …

Spanish consensus on the use of natalizumab (Tysabri®)-2013.

INTRODUCTION: Natalizumab treatment has been shown to be very efficacious in clinical trials and very effective in clinical practice in pati … e risk of PML should be stratified as high, medium, or low according to presence or absence of anti-JC virus antibodies, history of immunosuppressive therapy, and treatment duration. Although the presence of anti-JC virus antibodies is a significant finding, it should not be considered an absolute contraindication for natalizumab. This update provides gene …

JCPyV VP1 Mutations in Progressive MultifocalLeukoencephalopathy: Altering Tropismor Mediating Immune Evasion?

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 ce

Immunosuppression increases latent infection of brain by JC polyomavirus.

AIMS: Progressive multifocal leukoencephalopathy (PML) is caused by reactivation of JC polyomavirus (JCV). Increased JCV reactivation in kidney, as indicated by JCV viruria is reported during immunosuppression; however, the relevance of systemic to neural reactivation remains unknown. METHODS: Brain and kidney tissue from 138 non-PML patients (78 immunocompetent; 60 immunosuppressed) was assessed for JCV large T (LT) and viral protein (VP)1 DNA with nested PCR. Immunohistochemistry was performed to detect presence of JCV protein. Autopsy findings were reviewed and all brains underwent neuropa

Immune restoration diseases reflect diverse immunopathological mechanisms.

Up to one in four patients infected with human immunodeficiency virus type 1 and given antiretroviral therapy (ART) experiences inflammatory or cellular proliferative disease associated with a preexisting opportunistic infection, which may be subclinical. These immune restoration diseases (IRD) appear to result from the restoration of immunocompetence. IRD associated with intracellular pathogens are characterized by cellular immune responses and/or granulomatous inflammation. Mycobacterial and cryptococcal IRD are attributed to a pathological overproduction of Th1 cytokines. Clinicopathologica

Expression of major histocompatibility complex antigens in the brains of patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is caused by JC virus (JCV) infection of the central nervous system (CNS) in immunosuppressed patients. The immunopathogenesis of this chronic encephalitis is unknown. Because major histocompatibility (MHC) class I and class II antigens are important in modulating the immune response and viral clearance, we examined the tissue expression of MHC molecules in relation to CNS damage and presence of virus. By immunocytochemical staining, both MHC class I and class II antigens were expressed at high levels within PML lesions. Beta-2 microglobulin (be…

Cytomorphology of progressive multifocal leukoencephalopathy (PML): review of sixteen cases occurring in HIV-positive patients.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disorder of the central nervous system (CNS) resulting from infection of oligodendrocytes by JC virus. Although all patients immunocompromised by any congenital, acquired, or iatrogenic condition are at risk, the population which currently accounts for the majority of new cases is that infected with the human immunodeficiency virus (HIV). Though the clinical/radiologic presentation is characteristic, biopsy confirmation is necessary, as these patients are at risk for other primary CNS disorders which may produce similar …

Virus reactivations after autologous hematopoietic stem cell transplantation detected by multiplex PCR assay.

Several studies have indicated that viral reactivations following allogeneic hematopoietic stem cell transplantation (allo-HSCT) are frequen … ytomegalovirus (CMV), human herpesvirus 6 (HHV-6), HHV-7, HHV-8, adeno virus (ADV), BK virus (BKV), JC virus (JCV), parvovirus B19 (B19V), and hepatitis B virus (HBV).  Fifteen (63%) patients had at least one type of viral reactivation. HHV6 (n = 10; 41.7%) was most frequently detected followed by EBV (n = 7; 29.2%). HHV-6 peaked on day 21 after HSCT and p …

The Effect of Intravenous Methylprednisolone on Recurrent Exacerbation in Hematologic Malignancy-associated Progressive Multifocal Leukoencephalopathy.

We herein report a 65-year-old man with progressive multifocal leukoencephalopathy (PML) after 2-year remission from acute myeloid leukemia who developed recurrent episodes of left hemiparesis with gadolinium enhancement on magnetic resonance imaging. Steroid pulse therapy for each exacerbation induced clinical and radiological improvement, suggesting that exacerbations are an excessive immune response to the JC virus and distinct from immune reconstitution inflammatory syndrome (IRIS). Although glucocorticoids are recommended only for IRIS, steroid pulse therapy should be considered as a ther…

Inflammatory Cerebellar PML with a CD4/CD8 Ratio of 2.9 Showed a Favorable Prognosis in a Patient with Rheumatoid Arthritis.

The patient was a 74-year-old woman with rheumatoid arthritis who developed ataxia. MRI revealed T2-hyperintense lesions predominantly in the left middle cerebellar peduncle. Punctate or linear Gd enhancement was also observed on T1-weighted images. A brain biopsy was conducted and the pathology revealed a mild demyelinated lesion. Polymerase chain reaction (PCR) of biopsied brain tissues revealed the presence of JC virus (JCV) DNA, but JCV-infected oligodendroglia-like cells were not apparent on immunohistochemistry. Sensitive in-situ hybridization, however, detected three JCV-positive cells …

Progressive multifocal leukoencephalopathy 11 years after liver transplantation: a case report.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system caused by JC virus. Only ten cases of PML have been reported so far in liver transplant recipients. We present a case of liver posttransplantation PML with characteristic clinical and brain MRI findings, but with an atypical late onset, developed 11 years after transplantation and after single-drug, long-term (8 years), and low-dose (750 mg twice a day) immunosuppression with mycophenolate mofetil (MMF). This is the latest onset of PML associated to liver transplant reported. The presen…

Progressive multifocal leukoencephalopathy - immune reconstitution inflammatory syndrome (PML-IRIS) in liver transplant recipient.

65-year-old liver transplant recipient presented with progressive neurologic dysfunction. CSF analysis revealed high JC virus load and MRI findings suggested the diagnosis of progressive multifocal leukoencephalopathy (PML). Cidofovir and mirtazapine were initiated and patient's regular immunosuppressants were reduced. Subsequently patient developed left sided hemiplegia, drowsiness and severe neglect syndrome. MRI revealed enlargement of PML lesions with contrast enhancement and worsening of oedema, consistent with immune reconstitution inflammatory syndrome (IRIS). Steroids were initiated an…

Increased program cell death-1 expression on T lymphocytes of patients with progressive multifocal leukoencephalopathy.

The cellullar immune response is important in the containment of progressive multifocal leukoencephalopathy (PML). We examined program cell death-1 (PD-1) expression, a marker of cellular immune exhaustion, on T lymphocytes in PML. PD-1 expression was elevated on total CD4(+) and CD8(+) T cells (medians 36% and 24%) in PML patients compared with healthy control subjects (medians 14% and 18%; P = 0.0015 and P = 0.033). In PML patients, JC virus (JCV)-specific CD8(+) cytotoxic T lymphocytes expressed PD-1 more frequently than total CD8 T lymphocytes (means 39% and 78%, P = 0.0004). Blocking the …

Progressive multifocal leukoencephalopathy presenting as IRIS in an AIDS patient. A case report and literature review.

Progressive multifocal leukoencephalopathy causes an infection of the central nervous system by JC virus (JCV), a polyomavirus that destroys oligodendrocytes and their myelin processes. Here, we describe a patient with AIDS who developed a progressive multifocal leucoencephalopathy with the clinical and neuroimaging characteristics of the immune inflammatory reconstitution syndrome. Unlike other opportunistic infections, this disease can present when CD4 T cell counts are higher than those associated with AIDS and also when patients are receiving combined antiretroviral therapy. Clinical suspi…

An immunohistochemical study of p53 and proliferating cell nuclear antigen expression in progressive multifocal leukoencephalopathy.

Nuclear p53 immunoreactivity is demonstrated in infected oligodendroglia, as well as in a proportion of reactive and bizarre astrocytes, in seven progressive multifocal leukoencephalopathy (PML) biopsies. This likely represents binding to, and prolongation of the half-life of, wild-type p53 protein by JC virus T-antigen. Other possible mechanisms are considered. The same cells show proliferating cell nuclear antigen (PCNA) positivity, as do a proportion of morphologically normal oligodendroglia and astrocytes, reflecting proliferating populations of these glial sub-types. It is possible that f…

A report of progressive multifocal leukoencephalopathy during adjuvant abemaciclib for breast cancer.

Drugs inhibiting the cyclin-dependent kinases (CDK) 4 and 6 are widely used for the treatment of luminal breast cancer, in the adjuvant and in the metastatic setting, and adverse events are well-known. Progressive multifocal leukoencephalopathy (PML) is classically linked to immunosuppression. We present a case of progressive multifocal leukoencephalopathy that developed during adjuvant abemaciclib therapy in a seventy-year-old woman diagnosed with locally advanced ductal carcinoma of the breast. Neurological impairment developed after 18 months of initiating abemaciclib and in imaging tests a

Brain biopsy and pathological diagnosis for drug-associated progressive multifocal leukoencephalopathy (PML) with inflammatory reactions.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by JC virus (JCV) infection. Although recognized as an AIDS complication in the 1980s, PML has emerged as a serious adverse event of immunosuppressive therapies since 2005, particularly disease-modifying drugs (DMDs) for multiple sclerosis (MS). PML can also occur in patients with collagenous diseases receiving steroid therapy or with age-related immunosuppression. In some cases, the etiology of immunosuppression remains unclear. These cases often present with early manifestations o…