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Review
. 2016 Oct 25:7:1602.
doi: 10.3389/fmicb.2016.01602. eCollection 2016.

Epstein-Barr Virus: Diseases Linked to Infection and Transformation

Hem C Jha  1 , Yonggang Pei  1 , Erle S Robertson  1
Affiliations
Review

Epstein-Barr Virus: Diseases Linked to Infection and Transformation

Hem C Jha et al. Front Microbiol. .

Abstract

Epstein-Barr virus (EBV) was first discovered in 1964, and was the first known human tumor virus now shown to be associated with a vast number of human diseases. Numerous studies have been conducted to understand infection, propagation, and transformation in various cell types linked to human diseases. However, a comprehensive lens through which virus infection, reactivation and transformation of infected host cells can be visualized is yet to be formally established and will need much further investigation. Several human cell types infected by EBV have been linked to associated diseases. However, whether these are a direct result of EBV infection or indirectly due to contributions by additional infectious agents will need to be fully investigated. Therefore, a thorough examination of infection, reactivation, and cell transformation induced by EBV will provide a more detailed view of its contributions that drive pathogenesis. This undoubtedly expand our knowledge of the biology of EBV infection and the signaling activities of targeted cellular factors dysregulated on infection. Furthermore, these insights may lead to identification of therapeutic targets and agents for clinical interventions. Here, we review the spectrum of EBV-associated diseases, the role of the encoded latent antigens, and the switch to latency or lytic replication which occurs in EBV infected cells. Furthermore, we describe the cellular processes and critical factors which contribute to cell transformation. We also describe the fate of B-cells and epithelial cells after EBV infection and the expected consequences which contribute to establishment of viral-associated pathologies.

Keywords: B-cell; EBV; cancer; epithelial cell; infection; latency; lytic; transformation.

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Figures

FIGURE 1
FIGURE 1
(Left) Represents B-lymphocytes infection and (Right) epithelial cell infection. Epstein–Barr virus (EBV) infected B-lymphocytes and epithelial cells have pools of uninfected and infected cells. Further, some cells produce infectious virus which can infect new cells. The remaining cells will die through apoptosis and necrosis. A portion of the infected cells are transformed and leads to tumorigenesis through cell transformation. Some infected cells are also switched to a dormant stage and can be activated or reactivated when conditions are favorable for lytic replication.
FIGURE 2
FIGURE 2
Cell transformation and cell proliferation of tumor cell lines as mapped using the IPA software which demonstrates significant association with major cellular pathways. Here we have groups or complexes formed with cellular molecules including Rb, Skp2, CyclinD, the transcription factors E2F1, Tp73, Mdm2, Tp53, IRF4, Myc, HDAC1 and GMNN (Geminin), and kinases which include Aurora Kinase B, Pim1 and Gsk3B. We have also mapped the known regulation of these cellular antigens and their activities by the essential EBV latent antigens EBNA1, EBNA2, EBNA3C, and LMP1 for transformation and immortalization of EBV-infected cells leading to associated cancers.
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References

    1. Accardi R., Fathallah I., Gruffat H., Mariggio G., Le Calvez-Kelm F., Voegele C., et al. (2013). Epstein – Barr virus transforming protein LMP-1 alters B cells gene expression by promoting accumulation of the oncoprotein DeltaNp73alpha. PLoS Pathog. 9:e1003186 10.1371/journal.ppat.1003186 - DOI - PMC - PubMed
    1. Adamson A. L., Darr D., Holley-Guthrie E., Johnson R. A., Mauser A., Swenson J., et al. (2000). Epstein-Barr virus immediate-early proteins BZLF1 and BRLF1 activate the ATF2 transcription factor by increasing the levels of phosphorylated p38 and c-Jun N-terminal kinases. J. Virol. 74 1224–1233. 10.1128/JVI.74.3.1224-1233.2000 - DOI - PMC - PubMed
    1. Alexander F. E., Lawrence D. J., Freeland J., Krajewski A. S., Angus B., Taylor G. M., et al. (2003). An epidemiologic study of index and family infectious mononucleosis and adult Hodgkin’s disease (HD): evidence for a specific association with EBV+ve HD in young adults. Int. J. Cancer 107 298–302. 10.1002/ijc.11156 - DOI - PubMed
    1. Allday M. J. (2009). How does Epstein-Barr virus (EBV) complement the activation of Myc in the pathogenesis of Burkitt’s lymphoma? Semin. Cancer Biol. 19 366–376. 10.1016/j.semcancer.2009.07.007 - DOI - PMC - PubMed
    1. Allen U., Alfieri C., Preiksaitis J., Humar A., Moore D., Tapiero B., et al. (2002). Epstein-Barr virus infection in transplant recipients: summary of a workshop on surveillance, prevention and treatment. Can. J. Infect. Dis. 13 89–99. 10.1155/2002/634318 - DOI - PMC - PubMed