The Epstein-Barr Virus Oncogene EBNA1 Suppresses Natural Killer Cell Responses and Apoptosis Early after Infection of Peripheral B Cells

Smith, Danielle Westhoff; Chakravorty, Adityarup; Hayes, Mitchell; Hammerschmidt, Wolfgang; Sugden, Bill

doi:10.1128/mbio.02243-21

Cited by 26 publications

(12 citation statements)

References 86 publications

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“…Some of these are expressed during the lytic or prelatent phase, while others are more consistently expressed during the latent infection. For example, EBNA1 can induce CXCL12 to recruit regulatory T cells 69 and suppress NK cell responses by downregulating NKG2D ligands 70 . EBNA2 transcriptionally activates numerous genes involved in immune regulation, such as those encoding tumour necrosis factor (TNF) 71 , lymphotoxin-α 72 , IL-18R 73 and PDL1 (refs.…”

Section: Ebv Biology and Life Cyclementioning

confidence: 99%

Epstein–Barr virus and multiple sclerosis

2022

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Epstein–Barr virus (EBV) is a ubiquitous human lymphotropic herpesvirus with a well-established causal role in several cancers. Recent studies have provided compelling epidemiological and mechanistic evidence for a causal role of EBV in multiple sclerosis (MS). MS is the most prevalent chronic inflammatory and neurodegenerative disease of the central nervous system and is thought to be triggered in genetically predisposed individuals by an infectious agent, with EBV as the lead candidate. How a ubiquitous virus that typically leads to benign latent infections can promote cancer and autoimmune disease in at-risk populations is not fully understood. Here we review the evidence that EBV is a causal agent for MS and how various risk factors may affect EBV infection and immune control. We focus on EBV contributing to MS through reprogramming of latently infected B lymphocytes and the chronic presentation of viral antigens as a potential source of autoreactivity through molecular mimicry. We consider how knowledge of EBV-associated cancers may be instructive for understanding the role of EBV in MS and discuss the potential for therapies that target EBV to treat MS.

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Section: Ebv Biology and Life Cyclementioning

confidence: 99%

Epstein–Barr virus and multiple sclerosis

2022

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“…The role of KDMs in the development and function of NK cells Natural killer (NK) cells are cytotoxic lymphocytes that rapidly fight against pathogens to maintain homeostasis [100][101][102][103]. NK cells play important roles during early viral infection by releasing granules containing perforin and granzymes and secreting critical Fig.…”

Section: Functions Of Kdms In T Lymphocytes Developmentmentioning

confidence: 99%

Histone demethylases in the regulation of immunity and inflammation

Yin

Zhao

et al. 2023

Cell Death Discov.

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Pathogens or danger signals trigger the immune response. Moderate immune response activation removes pathogens and avoids excessive inflammation and tissue damage. Histone demethylases (KDMs) regulate gene expression and play essential roles in numerous physiological processes by removing methyl groups from lysine residues on target proteins. Abnormal expression of KDMs is closely associated with the pathogenesis of various inflammatory diseases such as liver fibrosis, lung injury, and autoimmune diseases. Despite becoming exciting targets for diagnosing and treating these diseases, the role of these enzymes in the regulation of immune and inflammatory response is still unclear. Here, we review the underlying mechanisms through which KDMs regulate immune-related pathways and inflammatory responses. In addition, we also discuss the future applications of KDMs inhibitors in immune and inflammatory diseases.

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“…On the contrary, expression in EBV − gastric carcinoma (GC) cells or other epithelial cell carcinomas of the LMP2A protein that is important for maintaining EBV latency and inducing host cell transformation, had a dual effect on the expression of MICA and MICB: LMP2A, on the one hand, upregulated their transcripts and, on the other hand, decreased total protein amounts, which resulted in a net reduction of both ligands at the cell membrane, though the functional consequences were not investigated [ 101 ]. Another recent work, using primary B cells infected with EBV either wt or deficient for the expression of the EBNA1 oncoprotein as well as epithelial cell lines transduced with EBNA1-expressing or control vector, showed that EBNA1 downregulated ULBP1 and ULBP5 mRNA levels, likely by reducing activation of cellular stress responses and c-Myc, and protected newly infected B cells from NKG2D-dependent killing by NK cells [ 102 ]. Finally, two independent works showed that EBV encodes for two distinct microRNAs targeting NKG2DL mRNA molecules, both belonging to the BART family and expressed in all forms of latency as well as during virus replication.…”

Section: Nk/ebv-infected Cell Interactionsmentioning

confidence: 99%

The Role of NK Cells in EBV Infection and Related Diseases: Current Understanding and Hints for Novel Therapies

Desimio

Covino

Rivalta

et al. 2023

Cancers

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The Epstein–Barr virus (EBV) is a ubiquitous herpesvirus most often transmitted during infancy and infecting the vast majority of human beings. Usually, EBV infection is nearly asymptomatic and results in life-long persistency of the virus in a latent state under the control of the host immune system. Yet EBV can cause an acute infectious mononucleosis (IM), particularly in adolescents, and is associated with several malignancies and severe diseases that pose a serious threat to individuals with specific inborn error of immunity (IEI). While there is a general consensus on the requirement for functional CD8 T cells to control EBV infection, the role of the natural killer (NK) cells of the innate arm of immunity is more enigmatic. Here we provide an overview of the interaction between EBV and NK cells in the immunocompetent host as well as in the context of primary and secondary immunodeficiencies. Moreover, we report in vitro data on the mechanisms that regulate the capacity of NK cells to recognize and kill EBV-infected cell targets and discuss the potential of recently optimized NK cell-based immunotherapies for the treatment of EBV-associated diseases.

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The Epstein-Barr Virus Oncogene EBNA1 Suppresses Natural Killer Cell Responses and Apoptosis Early after Infection of Peripheral B Cells

Abstract: Epstein-Barr virus (EBV) is a ubiquitous human pathogen, infecting up to 95% of the world’s adult population. Initial infection with EBV can cause infectious mononucleosis.

Cited by 26 publications

References 86 publications

Epstein–Barr virus and multiple sclerosis

Epstein–Barr virus and multiple sclerosis

Histone demethylases in the regulation of immunity and inflammation

The Role of NK Cells in EBV Infection and Related Diseases: Current Understanding and Hints for Novel Therapies

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