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Review
. 2023 Apr 2;15(7):2120.
doi: 10.3390/cancers15072120.

Contribution of Epstein-Barr Virus Lytic Proteins to Cancer Hallmarks and Implications from Other Oncoviruses

Mike Dorothea  1 , Jia Xie  1 , Stephanie Pei Tung Yiu  2   3 , Alan Kwok Shing Chiang  1
Affiliations
Review

Contribution of Epstein-Barr Virus Lytic Proteins to Cancer Hallmarks and Implications from Other Oncoviruses

Mike Dorothea et al. Cancers (Basel). .

Abstract

Epstein-Barr virus (EBV) is a prevalent human gamma-herpesvirus that infects the majority of the adult population worldwide and is associated with several lymphoid and epithelial malignancies. EBV displays a biphasic life cycle, namely, latent and lytic replication cycles, expressing a diversity of viral proteins. Among the EBV proteins being expressed during both latent and lytic cycles, the oncogenic roles of EBV lytic proteins are largely uncharacterized. In this review, the established contributions of EBV lytic proteins in tumorigenesis are summarized according to the cancer hallmarks displayed. We further postulate the oncogenic properties of several EBV lytic proteins by comparing the evolutionary conserved oncogenic mechanisms in other herpesviruses and oncoviruses.

Keywords: Epstein–Barr virus (EBV); cancer hallmarks; herpesvirus; lytic proteins; oncovirus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Contribution of EBV lytic proteins to hallmarks of cancers. EBV lytic proteins directly contribute to the hallmarks of avoiding immune destruction, activating invasion and metastasis, inducing or accessing vasculature, genome instability and mutation, resisting cell death, unlocking phenotypic plasticity and sustained proliferative signaling. Created with BioRender.com. Figure was adapted from “Hallmarks of Cancer: Circle” by BioRender.com (2023). Retrieved from https://app.biorender.com/biorender-templates, accessed on 23 February 2023.
Figure 2
Figure 2
Schematic diagram of the mechanisms employed by EBV to evade immune responses. Zta, BGLF5, BILF1, BNLF2a, BDLF3 and BCRF1 avoid immune surveillance by modulating the antigen presentation mechanisms. BCRF1 and BARF1 are inhibitory molecules that facilitate immune evasion. Rta, BHRF1, BGLF5, BLRF2 and BPLF1 evade innate immune responses by modulating various components of immune signaling pathways. Created with BioRender.com. Figure was adapted from “Icon Pack—Cytokine” and “cGAS-STING DNA Detection” by BioRender.com (2023). Retrieved from https://app.biorender.com/biorender-templates, accessed on 24 February 2023.
Figure 3
Figure 3
Schematic diagram of strategies of EBV in activating tissue invasion and metastasis, inducing or accessing vasculature, promoting genomic instability and mutation, resisting cell death and sustaining proliferative signaling. Zta, Rta, BILF1, BARF1, BALF1 and BALF3 induce tissue invasion, metastasis and angiogenesis. BMRF1, BKRF4, BALF3, BGLF4, BGLF5 and BNRF1 induce genomic instability and mutation through the inhibition of DNA damage response (DDR) and the formation of micronuclei and chromosomal instability. Zta, BARF1, BALF1 and BHRF1 promote cell survival via either cell death resistance or sustained proliferative signaling. Created with BioRender.com. Figure was adapted from “Tumor Vascularization” and “Extrinsic and Intrinsic Apoptosis” by BioRender.com (2023). Retrieved from https://app.biorender.com/biorender-templates, accessed on 24 February 2023.
Figure 4
Figure 4
Molecular mechanisms of BNRF1 and BMRF1 and their homologs of other oncoviruses in contributing to hallmarks of cancer. (A) BNRF1, HBV HBx, KSHV RTA and HPV E2 modulate DNA damage response (DDR) in cancer cells to promote genomic instability and mutation. (B) BMRF1 and KSHV PF-8 degrade PARP1 to inhibit DDR. Interaction between BMRF1 and NuRD may regulate both transcriptional activation and repression of cellular proteins enabling replicative immortality in cancer cells. KSHV PF-8 and HPV E7 can modulate the expression of PRMT5, UTX and UTY to promote epigenetic reprogramming. Created with BioRender.com.
Figure 5
Figure 5
Schematic diagram of EBV SM protein’s known and postulated contribution to cancer hallmarks. SM increases SUMOylation and STAT1 expression though its role in EBV oncogenesis is unclear. Several postulated hallmarks of cancer according to the function of SM homologs are inducing or accessing vasculature, resisting cell death, sustained proliferative signaling, enabling replicative immortality, senescent cells, genome instability and mutation and activating invasion and metastasis. Created with BioRender.com.
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References

    1. Epstein M., Achong B., Barr Y. Virus Particles in Cultured Lymphoblasts from Burkitt’s Lymphoma. Lancet. 1964;1:702–703. doi: 10.1016/S0140-6736(64)91524-7. - DOI - PubMed
    1. Chakravorty S., Yan B., Wang C., Wang L., Quaid J.T., Lin C.F., Briggs S.D., Majumder J., Canaria D.A., Chauss D., et al. Integrated Pan-Cancer Map of EBV-Associated Neoplasms Reveals Functional Host–Virus Interactions. Cancer Res. 2019;79:6010–6023. doi: 10.1158/0008-5472.CAN-19-0615. - DOI - PMC - PubMed
    1. Smatti M.K., Al-Sadeq D.W., Ali N.H., Pintus G., Abou-Saleh H., Nasrallah G.K. Epstein–Barr Virus Epidemiology, Serology, and Genetic Variability of LMP-1 Oncogene Among Healthy Population: An Update. Front. Oncol. 2018;8:211. doi: 10.3389/fonc.2018.00211. - DOI - PMC - PubMed
    1. Tsurumi T., Fujita M., Kudoh A. Latent and lytic Epstein-Barr virus replication strategies. Rev. Med. Virol. 2005;15:3–15. doi: 10.1002/rmv.441. - DOI - PubMed
    1. Hui K.F., Yiu S.P.T., Tam K.P., Chiang A.K.S. Viral-Targeted Strategies Against EBV-Associated Lymphoproliferative Diseases. Front. Oncol. 2019;9:81. doi: 10.3389/fonc.2019.00081. - DOI - PMC - PubMed

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