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Epstein-Barr virus and the origin of Hodgkin lymphoma.

Vockerodt M, Cader FZ, Shannon-Lowe C, Murray P - Chin J Cancer (2014)

Bottom Line: Although Epstein-Barr virus (EBV) is present in the malignant Hodgkin/Reed-Sternberg (HRS) cells of a proportion of cases of classical Hodgkin lymphoma (cHL), how the virus contributes to the pathogenesis of this disease remains poorly defined.It is clear from the studies of other EBV-associated cancers that the virus is usually not sufficient for tumor development and that other oncogenic co-factors are required.This article reviews what is known about the contribution of EBV to the pathogenesis of cHL and focuses on emerging evidence implicating chronic inflammation as a potential oncogenic co-factor in this malignancy.

View Article: PubMed Central - PubMed

Affiliation: School of Cancer Sciences, University of Birmingham, Birmingham, B15 2TT, the United Kingdom. p.g.murray@bham.ac.uk.

ABSTRACT
Although Epstein-Barr virus (EBV) is present in the malignant Hodgkin/Reed-Sternberg (HRS) cells of a proportion of cases of classical Hodgkin lymphoma (cHL), how the virus contributes to the pathogenesis of this disease remains poorly defined. It is clear from the studies of other EBV-associated cancers that the virus is usually not sufficient for tumor development and that other oncogenic co-factors are required. This article reviews what is known about the contribution of EBV to the pathogenesis of cHL and focuses on emerging evidence implicating chronic inflammation as a potential oncogenic co-factor in this malignancy.

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Related in: MedlinePlus

Loss of viral replication functions may promote the deve-lopment of Epstein-Barr virus (EBV)-positive classical Hodgkin lymphoma (cHL).Upper panel: in normal B cells, either B-cell receptor (BCR)- or latent membrane protein 2A (LMP2A)-mediated signaling can induce the EBV lytic cycle, ultimately leading to the release of infectious virions and eventual cell death. Lower panel: Hodgkin/Reed-Sternberg (HRS) cells lack not only a functional BCR but also essential components of the BCR signaling machinery such as Lyn and Syk and the transcription factor Egr1. Thus, BCR-negative germinal center (GC) B cells that also lack essential BCR signaling components might be positively selected during the development of cHL because they are protected from entry into the EBV replicative cycle and the ensuing cell death. LMP2A expression is retained in EBV-positive HRS cells, but it is not known how LMP2A signals in the absence of BCR signaling components.
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cjc-33-12-591-g001: Loss of viral replication functions may promote the deve-lopment of Epstein-Barr virus (EBV)-positive classical Hodgkin lymphoma (cHL).Upper panel: in normal B cells, either B-cell receptor (BCR)- or latent membrane protein 2A (LMP2A)-mediated signaling can induce the EBV lytic cycle, ultimately leading to the release of infectious virions and eventual cell death. Lower panel: Hodgkin/Reed-Sternberg (HRS) cells lack not only a functional BCR but also essential components of the BCR signaling machinery such as Lyn and Syk and the transcription factor Egr1. Thus, BCR-negative germinal center (GC) B cells that also lack essential BCR signaling components might be positively selected during the development of cHL because they are protected from entry into the EBV replicative cycle and the ensuing cell death. LMP2A expression is retained in EBV-positive HRS cells, but it is not known how LMP2A signals in the absence of BCR signaling components.

Mentions: In addition to existing in various latent states, EBV can also induce its replicative cycle in B cells, a process that eventually leads to the production of new viral particles or virions. The switch from latency to the replicative cycle is triggered by two distinct mechanisms—activation of BCR signaling and plasma cell differentiation, and the switch is regulated in part by the two latent membrane proteins. By providing a BCR-like signal, LMP2A induces entry into the viral replicative cycle[55],[56] (Figure 1). On the other hand, LMP1 prevents entry into the replicative cycle by suppressing plasma cell differentiation[57],[58].


Epstein-Barr virus and the origin of Hodgkin lymphoma.

Vockerodt M, Cader FZ, Shannon-Lowe C, Murray P - Chin J Cancer (2014)

Loss of viral replication functions may promote the deve-lopment of Epstein-Barr virus (EBV)-positive classical Hodgkin lymphoma (cHL).Upper panel: in normal B cells, either B-cell receptor (BCR)- or latent membrane protein 2A (LMP2A)-mediated signaling can induce the EBV lytic cycle, ultimately leading to the release of infectious virions and eventual cell death. Lower panel: Hodgkin/Reed-Sternberg (HRS) cells lack not only a functional BCR but also essential components of the BCR signaling machinery such as Lyn and Syk and the transcription factor Egr1. Thus, BCR-negative germinal center (GC) B cells that also lack essential BCR signaling components might be positively selected during the development of cHL because they are protected from entry into the EBV replicative cycle and the ensuing cell death. LMP2A expression is retained in EBV-positive HRS cells, but it is not known how LMP2A signals in the absence of BCR signaling components.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4308654&req=5

cjc-33-12-591-g001: Loss of viral replication functions may promote the deve-lopment of Epstein-Barr virus (EBV)-positive classical Hodgkin lymphoma (cHL).Upper panel: in normal B cells, either B-cell receptor (BCR)- or latent membrane protein 2A (LMP2A)-mediated signaling can induce the EBV lytic cycle, ultimately leading to the release of infectious virions and eventual cell death. Lower panel: Hodgkin/Reed-Sternberg (HRS) cells lack not only a functional BCR but also essential components of the BCR signaling machinery such as Lyn and Syk and the transcription factor Egr1. Thus, BCR-negative germinal center (GC) B cells that also lack essential BCR signaling components might be positively selected during the development of cHL because they are protected from entry into the EBV replicative cycle and the ensuing cell death. LMP2A expression is retained in EBV-positive HRS cells, but it is not known how LMP2A signals in the absence of BCR signaling components.
Mentions: In addition to existing in various latent states, EBV can also induce its replicative cycle in B cells, a process that eventually leads to the production of new viral particles or virions. The switch from latency to the replicative cycle is triggered by two distinct mechanisms—activation of BCR signaling and plasma cell differentiation, and the switch is regulated in part by the two latent membrane proteins. By providing a BCR-like signal, LMP2A induces entry into the viral replicative cycle[55],[56] (Figure 1). On the other hand, LMP1 prevents entry into the replicative cycle by suppressing plasma cell differentiation[57],[58].

Bottom Line: Although Epstein-Barr virus (EBV) is present in the malignant Hodgkin/Reed-Sternberg (HRS) cells of a proportion of cases of classical Hodgkin lymphoma (cHL), how the virus contributes to the pathogenesis of this disease remains poorly defined.It is clear from the studies of other EBV-associated cancers that the virus is usually not sufficient for tumor development and that other oncogenic co-factors are required.This article reviews what is known about the contribution of EBV to the pathogenesis of cHL and focuses on emerging evidence implicating chronic inflammation as a potential oncogenic co-factor in this malignancy.

View Article: PubMed Central - PubMed

Affiliation: School of Cancer Sciences, University of Birmingham, Birmingham, B15 2TT, the United Kingdom. p.g.murray@bham.ac.uk.

ABSTRACT
Although Epstein-Barr virus (EBV) is present in the malignant Hodgkin/Reed-Sternberg (HRS) cells of a proportion of cases of classical Hodgkin lymphoma (cHL), how the virus contributes to the pathogenesis of this disease remains poorly defined. It is clear from the studies of other EBV-associated cancers that the virus is usually not sufficient for tumor development and that other oncogenic co-factors are required. This article reviews what is known about the contribution of EBV to the pathogenesis of cHL and focuses on emerging evidence implicating chronic inflammation as a potential oncogenic co-factor in this malignancy.

Show MeSH
Related in: MedlinePlus