Chapter 5 : Pathogenesis of Epstein-Barr Virus

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Pathogenesis of Epstein-Barr Virus, Page 1 of 2

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Epstein-Barr virus (EBV) is a human DNA tumor virus with an extraordinarily diverse oncogenic potential. No other virus, human or otherwise, has shown the ability to contribute to malignant transformation in such a variety of cell backgrounds. Studies of EBV related malignancies in immunodeficiency states (posttransplant and AIDS) have provided insight into the significance in vivo of EBV-specific T-cell immunity, which has been studied so elegantly in vitro, in controlling primary and persistent EBV infection. Recent studies on tumor tissue from the EBV diseases have suggested that viral signaling, especially through the LMP1 protein, may directly contribute to the development and maintenance of the malignant phenotype. Novel strategies aimed at restoring antiviral T-cell immunity have shown promise in the postbone marrow transplant setting in controlling EBV-related lymphoproliferations. Future effort into better characterizing the role of EBV in T-lymphocyte malignancies and in non-lymphoid malignancies (Nasopharyngeal carcinoma (NPC) and smooth muscle tumors) will likely identify new pathogenic mechanisms utilized by this versatile virus that have yet to be appreciated in the better-studied EBV-related B-lymphoproliferative diseases.

Citation: Liebowitz D. 1998. Pathogenesis of Epstein-Barr Virus, p 175-199. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch5

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Restriction Fragment Length Polymorphism
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Figure 1

A model for the virus and cellular interactions that occur in primary EBV infection, persistence, and reactivation. Acute (primary [1°]) infection occurs in the oropharyngeal epithelium, and viral replication ensues. B lymphocytes are subsequently infected and display a latency type III viral gene expression pattern. At this point, the expanding population of EBV-infected B lymphoblasts are controlled by a primary CTL and NK cell response. EBV persistence is largely maintained in infected B cells that display a latency type I viral gene expression pattern. These cells may reactivate to a latency type II viral gene expression pattern, which is controlled by a secondary (memory) CTL response, or may be induced into lytic replication, where progeny virus may reinfect normal target tissues such as squamous epithelium and uninfected B lymphocytes. Details of the EBNA proteins and latent states are found in the text and in chapter 4.

Citation: Liebowitz D. 1998. Pathogenesis of Epstein-Barr Virus, p 175-199. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch5
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Image of Figure 2
Figure 2

A model for the progression of typical EBV-positive B-cell PTLD from “early” proliferative lesions to polymorphic PTLD and then to monomorphic PTLD, based on viral gene expression and cytogenetic data. Polymorphic lesions are usually polyclonal or oligoclonal, display a latency type III viral gene expression pattern, and do not have any cytogenetic evidence for cellular oncogene activation. Monomorphic lesions are monoclonal, also have a latency type III viral gene expression pattern, and frequently have recurring cytogenetic abnormalities. Moreover, the histologic subtype of the monomorphic lesions correlates with specific recurring cytogenetic abnormalities: approximately 70% of the monomorphic B-cell lesions had diffuse large-cell, immunoblastic (DLC-IB) histology and frequently had +11, +9, or 3q27 () recurring abnormalities; approximately 20% of the monomorphic B-cell lesions had small, non-cleaved, Burkitt-like (SNC-BL) histology and always had the t(8;14) or t(8;22) translocations involving ; 10% of the monomorphic B-cell lesions had diffuse large-cell, centroblastic (DLC-CB) histology and did not have recurring abnormalities. The continued expression of EBV proteins, such as the LMP1 transforming gene in the monomorphic PTLD lesions, suggests that these proteins play an important role in the progression and maintenance of the transformed phenotype. The association of specific recurring abnormalities with different monomorphic histologic subtypes indicates that cellular genetic features may ultimately determine the phenotype of monomorphic lesions.

Citation: Liebowitz D. 1998. Pathogenesis of Epstein-Barr Virus, p 175-199. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch5
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Table 1

Viral and cellular features of well-characterized EBV-associated malignancies

Citation: Liebowitz D. 1998. Pathogenesis of Epstein-Barr Virus, p 175-199. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch5

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