EBNA1, EBNA2, and EBNA3 link Epstein-Barr virus and hypovitaminosis D in multiple sclerosis pathogenesis

Marcucci, Samuel B.; Obeidat, Ahmed Z.

doi:10.1016/j.jneuroim.2019.577116

Cited by 16 publications

(19 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We set up the DBRs for vitamin D receptor (VDR), activation-induced cytidine deaminase (AID), Epstein Barr nuclear antigen 2 (EBNA2), Epstein Barr nuclear antigen 3 (EBNA3C), chosen among viral or host’s nuclear factors potentially associated to MS etiopathogenesis. 33–36 The DBRs for each nuclear factor were derived from recent literature (Supplementary Table 4) and matched with the GWAS-derived MS signals to confirm and expand previous results. We found statistically significant results for VDR, EBNA2, and AID for all the SNP position extensions (±50, 100, 200 kb), while for EBNA3C significant results came out at extension of ±100 and 200 kilobases.…”

Section: Resultssupporting

confidence: 59%

“…Therefore, we further inquired whether DNA regions plausibly coding for trRNA would share these features (i.e., they colocalize with such DRBs). We set up 4 new ROIs corresponding to the DBRs for VDR, activation-induced cytidine deaminase (AID), EBNA2, and Epstein Barr nuclear antigen 3 (EBNA3C), chosen among viral or host’s nuclear factors potentially associated to MS etiopathogenesis (Bäcker-Koduah et al, 2020; Marcucci & Obeidat, 2020; Sun et al, 2013). The DBRs for each nuclear factor were derived from recent literature (Supplementary Table S4) and matched with the GWAS-derived MS signals to confirm and expand previous results.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

GWAS associated Variants, Non-genetic Factors, and Transient Transcriptome in Multiple Sclerosis Etiopathogenesis: a Colocalization Analysis

Umeton

Bellucci

Bigi

et al. 2021

Preprint

View full text Add to dashboard Cite

A clinically actionable understanding of multiple sclerosis (MS) etiology goes through GWAS interpretation, prompting research on new gene regulatory models. Our previous works on these topics suggested a stochastic etiologic model where small-scale random perturbations could eventually reach a threshold for MS onset and progression. A new sequencing technology has mapped the transient transcriptome (TT), including intergenic RNAs, and antisense intronic RNAs. Through a rigorous colocalization analysis, here we show that genomic regions coding for the TT were significantly enriched for both MS-associated GWAS variants, and DNA binding sites for molecular transducers mediating putative, non-genetic, etiopathogenetic factors for MS (e.g., vitamin D deficiency, Epstein Barr virus latent infection, B cell dysfunction). These results suggest a model whereby TT-coding regions are hotspots of convergence between genetic ad non-genetic factors of risk/protection for MS (and plausibly for other complex disorders). Our colocalization analysis also provided a freely available data web interface at www.mscoloc.com for future research on transcriptional regulation in MS.

show abstract

Section: Resultssupporting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

GWAS associated Variants, Non-genetic Factors, and Transient Transcriptome in Multiple Sclerosis Etiopathogenesis: a Colocalization Analysis

Umeton

Bellucci

Bigi

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…In the 24-month period prior to the development of clinically isolated syndrome (CIS), our research group demonstrated that patients not only showed significantly lower 25(OH)D concentrations in comparison to healthy controls but that they also showed a gradual decrease in 25(OH)D concentrations as the incident of the first clinical manifestation of MS approached (108). 1,25(OH) 2 D 3 and the vitamin D receptor were also shown to interact with Epstein-Barr virus (EBV) nuclear antigens (EBNA), which are thought of as key contributors to MS pathogenesis (3,(109)(110)(111). It is hypothesized that hypovitaminosis D increases the autoimmune effects of EBV infection, thereby increasing the risk of developing MS because of the following reasons (111).…”

Section: Vitamin D Status and Its Association With Ms Riskmentioning

confidence: 99%

“…1,25(OH) 2 D 3 and the vitamin D receptor were also shown to interact with Epstein-Barr virus (EBV) nuclear antigens (EBNA), which are thought of as key contributors to MS pathogenesis (3,(109)(110)(111). It is hypothesized that hypovitaminosis D increases the autoimmune effects of EBV infection, thereby increasing the risk of developing MS because of the following reasons (111). First, in young MS patients, antibody reactivity against EBNA-1 increases with lower 25(OH)D levels (109).…”

Section: Vitamin D Status and Its Association With Ms Riskmentioning

confidence: 99%

A Brief Review of the Effects of Vitamin D on Multiple Sclerosis

et al. 2020

View full text Add to dashboard Cite

Multiple sclerosis (MS) is characterized as an autoimmune disease affecting the central nervous system. It is one of the most common neurological disorders in young adults. Over the past decades, increasing evidence suggested that hypovitaminosis D is a contributing factor to the risk of developing MS. From different risk factors contributing to the development of MS, vitamin D status is of particular interest since it is not only a modifiable risk factor but is also associated with MS disease activity. MS patients with lower serum vitamin D concentrations were shown to have higher disease activity. However, this finding does not demonstrate causality. In this regard, prospective vitamin D supplementation studies missed statistical significance in its primary endpoints but showed promising results in secondary outcome measures or post hoc analyses. An explanation for missed primary endpoints may be underpowered trials. Besides vitamin D supplementation as a potential add-on to long-term immunotherapeutic treatment, a recent laboratory study of our group pointed toward a beneficial effect of vitamin D to improve the efficacy of glucocorticoids in relapse therapy. In the following article, we will briefly review the effects of vitamin D on MS by outlining its effects on the immune and nervous system and by reviewing the association between vitamin D and MS risk as well as MS disease activity. We will also review the effects of vitamin D supplementation on MS risk and MS disease activity.

show abstract

“…During latent infection, the commonly expressed proteins include six nuclear antigens (EBV nuclear antigen [EBNA] 1, EBNA2, EBNA3A, EBNA3B, EBNA3C, and EBNALP), three membrane-associated proteins (latent membrane protein [LMP] 1, LMP2A, LMP2B), and two small non-coding RNAs (EBER1 and EBER2) ( Kerr, 2019 ; Li et al, 2020 ). EBNA1 (EBV nuclear antigen 1) plays a central role in maintaining viral genome replication and transcriptional regulation throughout the life cycle of the virus and is expressed in all EBV-infected cells ( Marcucci and Obeidat, 2020 ; Varvatsi et al, 2021 ). It binds to the viral genome of latent origin and completes viral self-replication within the host cells, which is favorable for establishing infection ( Sivachandran et al, 2012 ; Marcucci and Obeidat, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus and Neurological Diseases

Zhang

Zuo

Jiang

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

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.

show abstract

EBNA1, EBNA2, and EBNA3 link Epstein-Barr virus and hypovitaminosis D in multiple sclerosis pathogenesis

Cited by 16 publications

References 54 publications

GWAS associated Variants, Non-genetic Factors, and Transient Transcriptome in Multiple Sclerosis Etiopathogenesis: a Colocalization Analysis

GWAS associated Variants, Non-genetic Factors, and Transient Transcriptome in Multiple Sclerosis Etiopathogenesis: a Colocalization Analysis

A Brief Review of the Effects of Vitamin D on Multiple Sclerosis

Epstein-Barr Virus and Neurological Diseases

Contact Info

Product

Resources

About