Varicella-zoster virus encephalitis and vasculopathy in a patient treated with fingolimod.
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ABSTRACT:
SUBMITTER: Ratchford JN
PROVIDER: S-EPMC3484989 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceVaricella-zoster virus (VZV) infections increasingly are reported in patients with multiple sclerosis (MS) and constitute an area of significant concern, especially with the advent of more disease-modifying treatments in MS that affect T-cell-mediated immunity.ObjectiveTo assess the incidence, risk factors, and clinical characteristics of VZV infections in fingolimod-treated patients and provide recommendations for prevention and management.Design, setting, and participantsRates of VZV infections in fingolimod clinical trials are based on pooled data from the completed controlled phases 2 and 3 studies (3916 participants) and ongoing uncontrolled extension phases (3553 participants). Male and female patients aged 18 through 55 years (18-60 years for the phase 2 studies) and diagnosed as having relapsing-remitting MS were eligible to participate in these studies. In the postmarketing setting, reporting rates since 2010 were evaluated.InterventionsIn clinical trials, patients received fingolimod at a dosage of 0.5 or 1.25 mg/d, interferon beta-1a, or placebo. In the postmarketing setting, all patients received fingolimod, 0.5 mg/d (total exposure of 54,000 patient-years at the time of analysis).Main outcomes and measuresCalculation of the incidence rate of VZV infection per 1000 patient-years was based on the reporting of adverse events in the trials and the postmarketing setting.ResultsOverall, in clinical trials, VZV rates of infection were low but higher with fingolimod compared with placebo (11 vs 6 per 1000 patient-years). A similar rate was confirmed in the ongoing extension studies. Rates reported in the postmarketing settings were comparable (7 per 1000 patient-years) and remained stable over time. Disproportionality in reporting herpes zoster infection was higher for patients receiving fingolimod compared with those receiving other disease-modifying treatments (empirical Bayes geometric mean, 2.57 [90% CI, 2.26-2.91]); the proportion of serious herpes zoster infections was not higher than the proportion for other treatments (empirical Bayes geometric mean, 1.88 [90% CI, 0.87-3.70]). Corticosteroid treatment for relapses might be a risk factor for VZV reactivation.Conclusions and relevanceRates of VZV infections in clinical trials were low with fingolimod, 0.5 mg/d, but higher than in placebo recipients. Rates reported in the postmarketing setting are comparable. We found no sign of risk accumulation with longer exposure. Serious or complicated cases of herpes zoster were uncommon. We recommend establishing the patient's VZV immune status before initiating fingolimod therapy and immunization for patients susceptible to primary VZV infection. Routine antiviral prophylaxis is not needed, but using concomitant pulsed corticosteroid therapy beyond 3 to 5 days requires an individual risk-benefit assessment. Vigilance to identify early VZV symptoms is important to allow timely antiviral treatment.
| S-EPMC5391035 | biostudies-literature
Project description:BackgroundVaricella zoster virus (VZV) vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system infection produces amyloid.MethodsAβ peptides, amylin, and amyloid were measured in cerebrospinal fluid (CSF) from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin's function during infection, amylin was knocked down with small interfering RNA and viral complementary DNA (cDNA) was quantitated.ResultsCompared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aβ40 was reduced and Aβ42 unchanged. Intracellular amylin, Aβ42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA.ConclusionsVZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin.
| S-EPMC8030705 | biostudies-literature
Project description:An immunocompetent adult received corticosteroids for chest pain, which later was clinically found to be herpes zoster (HZ). She developed severe disease and rapid viral dissemination that elicited an exceptionally strong varicella zoster virus-specific B-cell and CD8 T-cell response. Clinicians should consider atypical HZ presentation prior to corticosteroid administration.
| S-EPMC7322817 | biostudies-literature
Project description:Primary infection by varicella zoster virus (VZV) typically results in childhood chickenpox, at which time latency is established in the neurons of the cranial nerve, dorsal root and autonomic ganglia along the entire neuraxis. During latency, the histone-associated virus genome assumes a circular episomal configuration from which transcription is epigenetically regulated. The lack of an animal model in which VZV latency and reactivation can be studied, along with the difficulty in obtaining high-titer cell-free virus, has limited much of our understanding of VZV latency to descriptive studies of ganglia removed at autopsy and analogy to HSV-1, the prototype alphaherpesvirus. However, the lack of miRNA, detectable latency-associated transcript and T-cell surveillance during VZV latency highlight basic differences between the two neurotropic herpesviruses. This article focuses on VZV latency: establishment, maintenance and reactivation. Comparisons are made with HSV-1, with specific attention to differences that make these viruses unique human pathogens.
| S-EPMC3118253 | biostudies-literature
Project description:The varicella zoster virus (VZV) is a latent viral infection and its reactivation has been reported following different conditions such as immunosuppression. This study presents a confirmed case of VZV encephalitis following the first dose administration of the Sinopharm COVID-19 vaccine. A 63-year-old immunocompetent woman who developed VZV encephalitis after first dose administration of Sinopharm COVID-19 vaccine. A final diagnosis of VZV encephalitis was made based on positive CSF PCR results for VZV infection. Treatment was administered with acyclovir and she returned to normal life without any neurological sequelae. In this report, VZV reactivation and VZV encephalitis have been observed after COVID-19 vaccination; however, the results of this report should be considered with some caution, and continued post-vaccine surveillance of adverse events is recommended to explore whether any causal association with VZV reactivation is biologically plausible in this context, or if it is just a coincidence.
| S-EPMC11002061 | biostudies-literature
Project description:Relationships among varicella-zoster virus (VZV; Human herpesvirus 3) genome sequences were examined to evaluate descent of strains, structures of lineages and incidence of recombination events. Eighteen complete, published genome sequences were aligned and 494 single nucleotide polymorphisms (SNPs) extracted, each as two alleles. At 281 SNPs, a single sequence differed from all the others. Distributions of the remaining 213 SNPs indicated that the sequences fell into five groups, which coincided with previously recognized phylogenetic groupings, termed E1, E2, J, M1 and M2. The 213-SNP set was divisible into 104 SNPs that were specific to a single group, and 109 cross-group SNPs that defined relationships among groups. This last set was evaluated by criteria of continuities in relationships between groups and breaks in such patterns, to identify crossover points and ascribe them to lineages. For the 99 cross-group SNPs in the genome's long unique region, it was seen that the E2 and M2 groups were almost completely distinct in their SNP alleles, and the E1 group was derived from a recombinant of E2 and M2. A valid phylogenetic tree could thus be constructed for the four E2 and two M2 strains. There was no substantive evidence for recombination within the E2 group or the E1 group (ten strains). The J and M1 groups each contained only one strain, and both were interpreted as having substantial distinct histories plus possible recombinant elements from the E2 and M2 lineages. The view of VZV recombination and phylogeny reached represents a major clarification of deep relationships among VZV lineages.
| S-EPMC2885040 | biostudies-literature
Project description: Not available
| S-EPMC3972264 | biostudies-literature
Project description:Herein we describe an episode of focal varicella-zoster virus (VZV) encephalitis in a healthy young man with neither rash nor radicular pain. The symptoms began with headaches and seizures, after which magnetic resonance imaging detected a single hyperintense lesion in the left temporal lobe. Because of the provisional diagnosis of a brain tumor, the lesion was excised and submitted for pathological examination. No tumor was found. But the tissue immunostained positively for VZV antigens, and wild-type VZV sequences were detected. In short, this case represents VZV reactivation, most likely in the trigeminal ganglion, in the absence of clinical herpes zoster.
| S-EPMC4202304 | biostudies-literature
Project description:In 1998, a varicella-zoster virus glycoprotein E (gE) mutant virus (VZV-MSP) was isolated from a child with chickenpox. VZV-MSP, representing a second VZV serotype, was considered a rarity. We isolated another VZV-MSP-like virus from an elderly man with herpes zoster. These gE mutant viruses may have arisen through independent mutation or may represent a distinct VZV subpopulation that emerged more than 50 years ago.
| S-EPMC2738511 | biostudies-literature
Project description:Varicella-zoster virus (VZV) causes clinically significant illness during acute and recurrent infection accompanied by robust innate and acquired immune responses. Innate immune cells in skin and ganglion secrete type I interferon (IFN-I) and proinflammatory cytokines to control VZV. Varicella-zoster virus subverts pattern recognition receptor sensing to modulate antigen presentation and IFN-I production. During primary infection, VZV hijacks T cells to disseminate to the skin and establishes latency in ganglia. Durable T- and B-cell memory formed within a few weeks of infection is boosted by reactivation or re-exposure. Antigen-specific T cells are recruited and potentially retained in VZV-infected skin to counteract reactivation. In latently VZV-infected ganglia, however, virus-specific T cells have not been recovered, suggesting that local innate immune responses control VZV latency. Antibodies prevent primary VZV infection, whereas T cells are fundamental to resolving disease, limiting severity, and preventing reactivation. In this study, we review current knowledge on the interactions between VZV and the human immune system.
| S-EPMC6151075 | biostudies-literature