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Regulation and dysregulation of Epstein-Barr virus latency: implications for the development of autoimmune diseases.
Autoimmunity 2008; 41(4):298-328A

Abstract

Epstein-Barr virus (EBV) is a human herpesvirus hiding in a latent form in memory B cells in the majority of the world population. Although, primary EBV infection is asymptomatic or causes a self-limiting disease, infectious mononucleosis, the virus is associated with a wide variety of neoplasms developing in immunosuppressed or immunodeficient individuals, but also in patients with an apparently intact immune system. In memory B cells, tumor cells, and lymphoblastoid cell lines (LCLs, transformed by EBV in vitro) the expression of the viral genes is highly restricted. There is no virus production (lytic viral replication associated with the expression of all viral genes) in tight latency. The expression of latent viral oncogenes and RNAs is under a strict epigenetic control via DNA methylation and histone modifications that results either in a complete silencing of the EBV genome in memory B cells, or in a cell-type dependent usage of latent promoters in tumor cells, germinal center B cells, and LCLs. Both the latent and lytic EBV proteins are potent immunogens and elicit vigorous B- and T-cell responses. In immunosuppressed and immunodeficient patients, or in individuals with a functional defect of EBV-specific T cells, lytic EBV replication is regularly activated and an increased viral load can be detected in the blood. Enhanced lytic replication results in new infection events and EBV-associated transformation events, and seems to be a risk factor both for malignant transformation and the development of autoimmune diseases. One may speculate that an increased load or altered presentation of a limited set of lytic or latent EBV proteins that cross-react with cellular antigens triggers and perpetuates the pathogenic processes that result in multiple sclerosis, systemic lupus erythematosus (SLE), and rheumatoid arthritis. In addition, in SLE patients EBV may cause defects of B-cell tolerance checkpoints because latent membrane protein 1, an EBV-encoded viral oncoprotein can induce BAFF, a B-cell activating factor that rescues self-reactive B cells and induces a lupus-like autoimmune disease in transgenic mice.

Authors+Show Affiliations

Department of Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

18432410

Citation

Niller, Hans Helmut, et al. "Regulation and Dysregulation of Epstein-Barr Virus Latency: Implications for the Development of Autoimmune Diseases." Autoimmunity, vol. 41, no. 4, 2008, pp. 298-328.
Niller HH, Wolf H, Minarovits J. Regulation and dysregulation of Epstein-Barr virus latency: implications for the development of autoimmune diseases. Autoimmunity. 2008;41(4):298-328.
Niller, H. H., Wolf, H., & Minarovits, J. (2008). Regulation and dysregulation of Epstein-Barr virus latency: implications for the development of autoimmune diseases. Autoimmunity, 41(4), pp. 298-328. doi:10.1080/08916930802024772.
Niller HH, Wolf H, Minarovits J. Regulation and Dysregulation of Epstein-Barr Virus Latency: Implications for the Development of Autoimmune Diseases. Autoimmunity. 2008;41(4):298-328. PubMed PMID: 18432410.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation and dysregulation of Epstein-Barr virus latency: implications for the development of autoimmune diseases. AU - Niller,Hans Helmut, AU - Wolf,Hans, AU - Minarovits,Janos, PY - 2008/4/25/pubmed PY - 2008/6/5/medline PY - 2008/4/25/entrez SP - 298 EP - 328 JF - Autoimmunity JO - Autoimmunity VL - 41 IS - 4 N2 - Epstein-Barr virus (EBV) is a human herpesvirus hiding in a latent form in memory B cells in the majority of the world population. Although, primary EBV infection is asymptomatic or causes a self-limiting disease, infectious mononucleosis, the virus is associated with a wide variety of neoplasms developing in immunosuppressed or immunodeficient individuals, but also in patients with an apparently intact immune system. In memory B cells, tumor cells, and lymphoblastoid cell lines (LCLs, transformed by EBV in vitro) the expression of the viral genes is highly restricted. There is no virus production (lytic viral replication associated with the expression of all viral genes) in tight latency. The expression of latent viral oncogenes and RNAs is under a strict epigenetic control via DNA methylation and histone modifications that results either in a complete silencing of the EBV genome in memory B cells, or in a cell-type dependent usage of latent promoters in tumor cells, germinal center B cells, and LCLs. Both the latent and lytic EBV proteins are potent immunogens and elicit vigorous B- and T-cell responses. In immunosuppressed and immunodeficient patients, or in individuals with a functional defect of EBV-specific T cells, lytic EBV replication is regularly activated and an increased viral load can be detected in the blood. Enhanced lytic replication results in new infection events and EBV-associated transformation events, and seems to be a risk factor both for malignant transformation and the development of autoimmune diseases. One may speculate that an increased load or altered presentation of a limited set of lytic or latent EBV proteins that cross-react with cellular antigens triggers and perpetuates the pathogenic processes that result in multiple sclerosis, systemic lupus erythematosus (SLE), and rheumatoid arthritis. In addition, in SLE patients EBV may cause defects of B-cell tolerance checkpoints because latent membrane protein 1, an EBV-encoded viral oncoprotein can induce BAFF, a B-cell activating factor that rescues self-reactive B cells and induces a lupus-like autoimmune disease in transgenic mice. SN - 1607-842X UR - https://www.unboundmedicine.com/medline/citation/18432410/Regulation_and_dysregulation_of_Epstein_Barr_virus_latency:_implications_for_the_development_of_autoimmune_diseases_ L2 - http://www.tandfonline.com/doi/full/10.1080/08916930802024772 DB - PRIME DP - Unbound Medicine ER -