Epstein-Barr virus infection in the development of neurological disorders

Soldan, Samantha S.; Lieberman, Paul M.

doi:10.1016/j.ddmod.2020.01.001

Cited by 36 publications

(35 citation statements)

References 241 publications

(205 reference statements)

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“…Furthermore, the CD8 + CD28 − CD57 + T-cells have a central role in the immune response to EBV-induced MS. During EBV infection, the increased CD8 + CD28 − CD57 + T-cells upregulate PD-1 expression, increase IFN-γ release, inhibit the conversion of EBV-infected B-cells to memory cells and induce the development of MS ( Cencioni et al, 2017 ). Moreover, EBV-infected B-cells and plasma cells accumulate in the brains of patients with MS ( Soldan and Lieberman, 2020 ; Ioannides et al, 2021 ). Similarly, the accumulation of EBV-positive B-cells was observed patients with RRMS ( Houen et al, 2020 ).…”

Section: Ebv and Multiple Sclerosismentioning

confidence: 99%

“…EBV infection can be the main manifestation of acute cerebellar ataxia ( Ali and Lawthom, 2013 ). Patients are seropositive for EBV IgM and IgG, and OCBs of EBV viral capsid antigen antibodies can be found in the CSF( Al-Shokri et al, 2020 ; Soldan and Lieberman, 2020 ). EBV infection mainly affects the cerebral hemispheres and leads to hydrocephalus and increased intracranial pressure ( Geurten et al, 2018 ).…”

Section: Ebv and Acute Cerebellar Ataxiamentioning

confidence: 99%

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Epstein-Barr Virus and Neurological Diseases

Zhang

Zuo

Jiang

et al. 2022

Front. Mol. Biosci.

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Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a double-stranded DNA virus that is ubiquitous in 90–95% of the population as a gamma herpesvirus. It exists in two main states, latent infection and lytic replication, each encoding viral proteins with different functions. Human B-lymphocytes and epithelial cells are EBV-susceptible host cells. EBV latently infects B cells and nasopharyngeal epithelial cells throughout life in most immunologically active individuals. EBV-infected cells, free viruses, their gene products, and abnormally elevated EBV titers are observed in the cerebrospinal fluid. Studies have shown that EBV can infect neurons directly or indirectly via infected B-lymphocytes, induce neuroinflammation and demyelination, promote the proliferation, degeneration, and necrosis of glial cells, promote proliferative disorders of B- and T-lymphocytes, and contribute to the occurrence and development of nervous system diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, acute cerebellar ataxia, meningitis, acute disseminated encephalomyelitis, and brain tumors. However, the specific underlying molecular mechanisms are unclear. In this paper, we review the mechanisms underlying the role of EBV in the development of central nervous system diseases, which could bebeneficial in providing new research ideas and potential clinical therapeutic targets for neurological diseases.

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Section: Ebv and Multiple Sclerosismentioning

confidence: 99%

Section: Ebv and Acute Cerebellar Ataxiamentioning

confidence: 99%

Epstein-Barr Virus and Neurological Diseases

Zhang

Zuo

Jiang

et al. 2022

Front. Mol. Biosci.

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“…Indeed, compliment receptor 2 (CR2), the primary receptor for EBV, is expressed on astrocytes, and upon viral entry, astrocytes demonstrate increased proliferation [ 30 , 31 ]. EBV’s association with a plethora of CNS indications including, but not limited to, ataxia, encephalitis, and demyelinating diseases, as well as its frequent presence in CNS lymphomas, has prompted inquiry into its role in gliomagenesis [ 32 , 33 ]. However, results thus far have been discordant and point to no clear role for EBV in GBM [ 34 ].…”

Section: Endogenous Viruses Found In Gbmmentioning

confidence: 99%

Viral Control of Glioblastoma

Mihelson

McGavern

2021

Viruses

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Glioblastoma multiforme (GBM) is a universally lethal cancer of the central nervous system. Patients with GBM have a median survival of 14 months and a 5-year survival of less than 5%, a grim statistic that has remained unchanged over the last 50 years. GBM is intransigent for a variety of reasons. The immune system has a difficult time mounting a response against glioblastomas because they reside in the brain (an immunologically dampened compartment) and generate few neoantigens relative to other cancers. Glioblastomas inhabit the brain like sand in the grass and display a high degree of intra- and inter-tumoral heterogeneity, impeding efforts to therapeutically target a single pathway. Of all potential therapeutic strategies to date, virotherapy offers the greatest chance of counteracting each of the obstacles mounted by GBM. Virotherapy can xenogenize a tumor that is deft at behaving like “self”, triggering adaptive immune recognition in an otherwise immunologically quiet compartment. Viruses can also directly lyse tumor cells, creating damage and further stimulating secondary immune reactions that are detrimental to tumor growth. In this review, we summarize the basic immune mechanisms underpinning GBM immune evasion and the recent successes achieved using virotherapies.

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“…Central nervous system (CNS) complications from EBV infection have long been appreciated (reviewed in [ 21 ] and the earliest descriptions of Burkitt’s lymphoma suggest that most patients (21/25 in an early autopsy series) had tumors involving the brain or meninges [ 22 ]. Other malignancies involving EBV infected B cells in the CNS include PCNSL, a primary intracranial tumor of B-cell origin that accounts for 1% of all lymphomas and 3–5% of primary brain tumors [ 23 , 24 ] and is commonly, though not exclusively, observed in patients who are immunocompromised.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes

Soldan

Lamontagne

et al. 2021

PLoS Pathog

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Subpopulations of B-lymphocytes traffic to different sites and organs to provide diverse and tissue-specific functions. Here, we provide evidence that epigenetic differences confer a neuroinvasive phenotype. An EBV+ B cell lymphoma cell line (M14) with low frequency trafficking to the CNS was neuroadapted to generate a highly neuroinvasive B-cell population (MUN14). MUN14 B cells efficiently infiltrated the CNS within one week and produced neurological pathologies. We compared the gene expression profiles of viral and cellular genes using RNA-Seq and identified one viral (EBNA1) and several cellular gene candidates, including secreted phosphoprotein 1/osteopontin (SPP1/OPN), neuron navigator 3 (NAV3), CXCR4, and germinal center-associated signaling and motility protein (GCSAM) that were selectively upregulated in MUN14. ATAC-Seq and ChIP-qPCR revealed that these gene expression changes correlated with epigenetic changes at gene regulatory elements. The neuroinvasive phenotype could be attenuated with a neutralizing antibody to OPN, confirming the functional role of this protein in trafficking EBV+ B cells to the CNS. These studies indicate that B-cell trafficking to the CNS can be acquired by epigenetic adaptations and provide a new model to study B-cell neuroinvasion associated CNS lymphoma and autoimmune disease of the CNS, including multiple sclerosis (MS).

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Epstein-Barr virus infection in the development of neurological disorders

Cited by 36 publications

References 241 publications

Epstein-Barr Virus and Neurological Diseases

Epstein-Barr Virus and Neurological Diseases

Viral Control of Glioblastoma

Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes

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