The interplay between Epstein-Bar virus (EBV) with the p53 and its homologs during EBV associated malignancies

Abstract

p53, p63, and p73, the members of the p53 family of proteins, are structurally similar proteins that play central roles regulating cell cycle and apoptotic cell death. Alternative splicing at the carboxyl terminus and the utilization of different promoters further categorizes these proteins as having different isoforms for each. Among such isoforms, TA and ΔN versions of each protein serve as the pro and the anti-apoptotic proteins, respectively. Changes in the expression patterns of these isoforms are noted in many human cancers. Proteins of certain human herpesviruses, like Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), interact with p53 family members and alter their expressions in many malignancies. Upon infections in the B cells and epithelial cells, EBV expresses different lytic or latent proteins during viral replication and latency respectively to preserve viral copy number, chromosomal integrity and viral persistence inside the host. In this review, we have surveyed and summarised the interactions of EBV gene products, known so far, with the p53 family proteins. The interactions between P53 and EBV oncoproteins are observed in stomach cancer, non-Hodgkin's lymphoma (NHL) of the head and neck, Nasopharyngeal Cancer (NPC), Gastric carcinoma (GC) and Burkitt's lymphoma (BL). EBV latent protein EBNA1, EBNA3C, LMP-1, and lytic proteins BZLF-1 can alter p53 expressions in many cancer cell lines. Interactions of p63 with EBNA-1, 2, 5, LMP-2A and BARF-1 have also been investigated in several cancers. Similarly, associations of p73 isoform with EBV latent proteins EBNA3C and LMP-1 have been reported. Methylation and single nucleotide polymorphisms in p53 have also been found to be correlated with EBV infection. Therefore, interactions and altered expression strategies of the isoforms of p53 family proteins in EBV associated cancers propose an important field for further molecular research.

Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA

“…p53 mutation is very common in ovarian cancer, particularly in high-grade serous ovarian carcinoma. NPC cells usually have wild-type p53, however, NPC is highly associated with Epstein-Bar virus that can inactivate p53 [32]. Cervical cancer Hela cell line is also known for having p53 inactivated by human papillomavirus proteins [33].…”

EBV-Positive Gastric Cancer: Current Knowledge and Future Perspectives

“…Tumor protein p53, or simply p53, is closely related to the occurrence of gastric cancer, and many studies find EBV infection to be associated with p53 methylation ( 21 – 23 ). In 2019, Camargo et al.…”

Factors in Oncogenesis: Viral Infections in Ovarian Cancer

“…An EBV viral miRNA, miR-BART7, induces cisplatin resistance and develops resistance to first-line chemotherapy and early death in patients with serous OC [76]. EBV nuclear antigens (EBNAs) and membrane proteins (LMP1, LMP2A, and LMP2B) are known target the p53 family in lymphomas and nasopharyngeal and gastric cancer [168]. However, the association between EBV and p53 isoforms in OC is yet to be defined.…”