Epstein-Barr Virus (EBV)-Related Lymphoproliferative Disorders in Ataxia Telangiectasia: Does ATM Regulate EBV Life Cycle?
Epstein-Barr virus (EBV) is an ubiquitous herpesvirus with a tropism for epithelial cells (where lytic replication occurs) and B-cells (where latency is maintained). EBV persists throughout life and chronic infection is asymptomatic in most individuals. However, immunocompromised patients may be una...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.03060/full |
| _version_ | 1819263632091906048 |
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| author | Moussab Tatfi Olivier Hermine Felipe Suarez |
| author_facet | Moussab Tatfi Olivier Hermine Felipe Suarez |
| author_sort | Moussab Tatfi |
| collection | DOAJ |
| description | Epstein-Barr virus (EBV) is an ubiquitous herpesvirus with a tropism for epithelial cells (where lytic replication occurs) and B-cells (where latency is maintained). EBV persists throughout life and chronic infection is asymptomatic in most individuals. However, immunocompromised patients may be unable to control EBV infection and are at increased risk of EBV-related malignancies, such as diffuse large B-cell lymphomas or Hodgkin's lymphomas. Ataxia telangiectasia (AT) is a primary immunodeficiency caused by mutations in the ATM gene and associated with an increased incidence of cancers, particularly EBV-associated lymphomas. However, the immune deficiency present in AT patients is often too modest to explain the increased incidence of EBV-related malignancies. The ATM defect in these patients could therefore impair the normal regulation of EBV latency in B-cells, thus promoting lymphomagenesis. This suggests that ATM plays a role in the normal regulation of EBV latency. ATM is a serine/threonine kinase involved in multiple cell functions such as DNA damage repair, cell cycle regulation, oxidative stress, and gene expression. ATM is implicated in the lytic cycle of EBV, where EBV uses the activation of DNA damage repair pathway to promote its own replication. ATM regulates the latent cycle of the EBV-related herpesvirus KSHV and MHV68. However, the contribution of ATM in the control of the latent cycle of EBV is not yet known. A better understanding of the regulation of EBV latency could be harnessed in the conception of novel therapeutic strategies in AT and more generally in all ATM deficient EBV-related malignancies. |
| first_indexed | 2024-12-23T20:16:40Z |
| format | Article |
| id | doaj.art-88066cc97b6c465490d4304cfb504f3e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T20:16:40Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-88066cc97b6c465490d4304cfb504f3e2022-12-21T17:32:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-01-01910.3389/fimmu.2018.03060426262Epstein-Barr Virus (EBV)-Related Lymphoproliferative Disorders in Ataxia Telangiectasia: Does ATM Regulate EBV Life Cycle?Moussab TatfiOlivier HermineFelipe SuarezEpstein-Barr virus (EBV) is an ubiquitous herpesvirus with a tropism for epithelial cells (where lytic replication occurs) and B-cells (where latency is maintained). EBV persists throughout life and chronic infection is asymptomatic in most individuals. However, immunocompromised patients may be unable to control EBV infection and are at increased risk of EBV-related malignancies, such as diffuse large B-cell lymphomas or Hodgkin's lymphomas. Ataxia telangiectasia (AT) is a primary immunodeficiency caused by mutations in the ATM gene and associated with an increased incidence of cancers, particularly EBV-associated lymphomas. However, the immune deficiency present in AT patients is often too modest to explain the increased incidence of EBV-related malignancies. The ATM defect in these patients could therefore impair the normal regulation of EBV latency in B-cells, thus promoting lymphomagenesis. This suggests that ATM plays a role in the normal regulation of EBV latency. ATM is a serine/threonine kinase involved in multiple cell functions such as DNA damage repair, cell cycle regulation, oxidative stress, and gene expression. ATM is implicated in the lytic cycle of EBV, where EBV uses the activation of DNA damage repair pathway to promote its own replication. ATM regulates the latent cycle of the EBV-related herpesvirus KSHV and MHV68. However, the contribution of ATM in the control of the latent cycle of EBV is not yet known. A better understanding of the regulation of EBV latency could be harnessed in the conception of novel therapeutic strategies in AT and more generally in all ATM deficient EBV-related malignancies.https://www.frontiersin.org/article/10.3389/fimmu.2018.03060/fullataxia telangiectasiaEpstein Barr viruslatencyB-cellprimary immune deficiencylymphomagenesis |
| spellingShingle | Moussab Tatfi Olivier Hermine Felipe Suarez Epstein-Barr Virus (EBV)-Related Lymphoproliferative Disorders in Ataxia Telangiectasia: Does ATM Regulate EBV Life Cycle? Frontiers in Immunology ataxia telangiectasia Epstein Barr virus latency B-cell primary immune deficiency lymphomagenesis |
| title | Epstein-Barr Virus (EBV)-Related Lymphoproliferative Disorders in Ataxia Telangiectasia: Does ATM Regulate EBV Life Cycle? |
| title_full | Epstein-Barr Virus (EBV)-Related Lymphoproliferative Disorders in Ataxia Telangiectasia: Does ATM Regulate EBV Life Cycle? |
| title_fullStr | Epstein-Barr Virus (EBV)-Related Lymphoproliferative Disorders in Ataxia Telangiectasia: Does ATM Regulate EBV Life Cycle? |
| title_full_unstemmed | Epstein-Barr Virus (EBV)-Related Lymphoproliferative Disorders in Ataxia Telangiectasia: Does ATM Regulate EBV Life Cycle? |
| title_short | Epstein-Barr Virus (EBV)-Related Lymphoproliferative Disorders in Ataxia Telangiectasia: Does ATM Regulate EBV Life Cycle? |
| title_sort | epstein barr virus ebv related lymphoproliferative disorders in ataxia telangiectasia does atm regulate ebv life cycle |
| topic | ataxia telangiectasia Epstein Barr virus latency B-cell primary immune deficiency lymphomagenesis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.03060/full |
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