Expression of human cytomegalovirus components in the brain tissues of patients with Rasmussen’s encephalitis

Zhang, Yao; Wang, Yisong; Chen, Sichang; Chen, Shuai; Guan, Yuguang; Liu, Changqing; Li, Tianfu; Luan, Guoming; An, Jing

doi:10.1007/s12250-016-3917-z

Cited by 6 publications

(15 citation statements)

References 26 publications

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“…It has been reported that several viral antigens can be detected in the human central nervous system, including in the endosomes of immune cells and neurons (Bsibsi et al, 2002). Previously, others and we reported the detection of HCMV, HSV-1, and EBV in RE brain tissues (Walter and Renella, 1989;Farrell et al, 1991;Zhang et al, 2017). Because TLR3 and TLR9 are important PRRs for DNA viruses, it is speculated that the TLR3 signal pathway is activated by viral dsRNA through TRIF, a downstream molecule of TLR3, leading to the release of proinflammatory cytokines and tissue injury.…”

Section: Introductionmentioning

confidence: 80%

“…A total of 26 patients with RE, admitted to Sanbo Brain Hospital from April 2008 to December 2013, were enrolled in the study (Zhang et al, 2017). Clinical diagnosis was made according to the European diagnostic criteria (Bien et al, 2005).…”

Section: Patient Cohort and Brain Sample Collectionmentioning

confidence: 99%

“…Paraffin sections were treated according to a routine IHC method (Zhang et al, 2017). After removing paraffin, sections were incubated with 3% peroxide-methanol and 1% bovine serum albumin for blocking endogenous peroxidase activity and nonspecific antibody binding sites, respectively.…”

Section: Immune Histo-chemistry (Ihc) Stainingmentioning

confidence: 99%

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Elevated expression of EBV and TLRs in the brain is associated with Rasmussen’s encephalitis

Wang

Liu

et al. 2017

Virol. Sin.

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Rasmussen's encephalitis (RE) is a rare pediatric neurological disorder, the etiology of which remains unclear. It has been speculated that the immunopathogenesis of RE involves damage to neurons, which eventually leads to the occurrence of RE. Viral infection may be a critical factor in triggering RE immunopathogenesis. In this study, we analyzed the expression of Epstein-Barr virus (EBV) antigens as well as of Toll-like receptor 3 (TLR3), TLR9, and downstream adapter TIRdomain-containing adapter-inducing interferon-β (TRIF) in the brain tissues of 26 patients with RE and 16 control individuals using immunohistochemistry (IHC). In the RE group, EBV antigens were detected in 53% of individuals at various expression levels. In contrast, there was no detectable EBV antigen expression in control brain tissues. Moreover, we found marked increases in the expression of TLR3, TLR9, and TRIF in the brain tissues of RE patients compared with levels in the control group. Furthermore, among RE cases, EBV expression and high TLR3 expression were associated with more severe brain atrophy. Our results suggest that the elevated expression of EBV and TLRs may be involved in RE occurrence through the activation of downstream molecules.

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Section: Introductionmentioning

confidence: 80%

Section: Patient Cohort and Brain Sample Collectionmentioning

confidence: 99%

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Elevated expression of EBV and TLRs in the brain is associated with Rasmussen’s encephalitis

Wang

Liu

et al. 2017

Virol. Sin.

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“…Over the years, several studies have reported the detection of a number of viruses, including enteroviruses, EBV, human HCMV, human papillomavirus and herpes simplex virus (HSV), in the brains of RE patients (Pardo et al, 2014). Furthermore, in our previous research, antigens of various human herpesviruses (HHVs), including HCMV, EBV and HHV6, were detected in RE brain tissues with positive rates ranging from 50 to 88.5% (Zhang et al, 2017;Liu et al, 2018). In addition, it was found that the interferon-induced transmembrane protein-3 (IFITM3) polymorphism rs12252-C is associated with the high detection rate of HCMV and rapid disease progression in RE patients with the IFITM3 rs12252-CC genotype.…”

Section: Discussionmentioning

confidence: 87%

Genetic Factors in Rasmussen’s Encephalitis Characterized by Whole-Exome Sequencing

Wang

Liu

et al. 2021

Front. Neurosci.

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Rasmussen’s encephalitis (RE) is a rare chronic neurological disorder characterized by unihemispheric brain atrophy and epileptic seizures. The mechanisms of RE are complex. Adaptive immunity, innate immunity and viral infection are all involved in the development of RE. However, there are few studies on the role of genetic factors in the mechanisms of RE. Thus, the objective of this study was to reveal the genetic factors in the mechanisms of RE. Whole-exome sequencing (WES) was performed in 15 RE patients. Ten patients with temporal lobe epilepsy (TLE), which is a common and frequently intractable seizure disorder, were used as the controls. Thirty-one non-silent single nucleotide variants (SNVs) affecting 16 genes were identified in the RE cases. The functions of the genes with SNVs were associated with antigen presentation, antiviral infection, epilepsy, schizophrenia and nerve cell regeneration. Genetic factors of RE were found first in this study. These results suggest that RE patients have congenital abnormalities in adaptive immunity and are susceptible to some harmful factors, which lead to polygenic abnormal disease.

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“…Our epilepsy center suggested that expression of Epstein-Barr virus antigen, human cytomegalovirus antigen, human herpes virus 6 antigen, and human papilloma virus antigen was obvious in RE brain. 32 – 35 However, virus infection mechanisms could not illustrate the pathogenesis adequately and no study has detected virus replication in brain tissue of RE patients up to now. The reasons underlying virus antigen expression in RE need further investigation.…”

Section: Etiology and Pathogenesismentioning

confidence: 99%

Rasmussen’s encephalitis: mechanisms update and potential therapy target

Tang

Luan

2020

Therapeutic Advances in Chronic Disease

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Rasmussen’s encephalitis (RE) is rare neurological diseases characterized as epilepsia partialis continua, invariably hemiparesis, and cognitive impairment. This disease is encountered frequently in childhood and presents with progressive atrophy of the unilateral hemisphere, and there are also sustained neurological complications. Owing to uncertain pathogenesis, the most effective way to limit the influence of seizures currently is cerebral hemispherectomy. In this review, we focus on four main lines of pathogenesis: virus infection, antibody-mediated, cell-mediated immunity, and microglia activation. Although one or more antigenic epitopes may give rise to infiltrating T cell responses in RE brain tissue, no exact antigen was confirmed as the definite cause of the disease. On the other hand, the appearance of antibodies related with RE seem to be a secondary pathological process. Synthetic studies have suggested an adaptive immune mechanism mediated by CD8+ T cells and an innate immune mechanism mediated by activated microglia and neuroglia. Accordingly, opinions have been raised that immunomodulatory treatments aimed at initial damage to the brain that are induced by cytotoxic CD8+ T cell lymphocytes and microglia in the early stage of RE slow down disease progression. However, systematic exploration of the theory behind these therapeutic effects based on multicenter and large sample studies are needed. In addition, dysfunction of the adenosine system, including the main adenosine removing enzyme adenosine kinase and adenosine receptors, has been demonstrated in RE, which might provide a novel therapeutic target for treatment of RE in future.

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Expression of human cytomegalovirus components in the brain tissues of patients with Rasmussen’s encephalitis

Cited by 6 publications

References 26 publications

Elevated expression of EBV and TLRs in the brain is associated with Rasmussen’s encephalitis

Elevated expression of EBV and TLRs in the brain is associated with Rasmussen’s encephalitis

Genetic Factors in Rasmussen’s Encephalitis Characterized by Whole-Exome Sequencing

Rasmussen’s encephalitis: mechanisms update and potential therapy target

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