Ebna1

Abstract

Epstein-Barr nuclear antigen 1 (EBNA1) plays multiple important roles in EBV latent infection and has also been shown to impact EBV lytic infection. EBNA1 is required for the stable persistence of the EBV genomes in latent infection and activates the expression of other EBV latency genes through interactions with specific DNA sequences in the viral episomes. EBNA1 also interacts with several cellular proteins to modulate the activities of multiple cellular pathways important for viral persistence and cell survival. These cellular effects are also implicated in oncogenesis, suggesting a direct role of EBNA1 in the development of EBV-associated tumors.

More than just oncogenes: mechanisms of tumorigenesis by human viruses

“…EBV and KSHV also encode several proteins that contribute to oncogenesis. In EBV these include the Epstein Barr nuclear antigen proteins (EBNAs) and the latent membrane proteins (LMP1 and 2), and in KSHV the latent nuclear antigen (LANA), and the signaling proteins vGPCR, K1, K15, kaposin B, vCyclin and vFLIP [37–47]. These KSHV and EBV proteins up-regulate expression of oncogenic cellular proteins and microRNAs, down-regulate tumor suppressor expression and activate signaling pathways, like the NF-κB pathway, that promote growth and proliferation of B cells and endothelial cells, the cells that give rise to EBV- and KSHV-induced tumors [48].…”

Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to G-quadruplexes of EBNA1 mRNA

“…Another example is the nasopharyngeal carcinoma, which is particularly frequent among men in China and Tunisia. Like all the gammaherpesviruses, EBV evades the host immune system but has an Achilles heel: its genome maintenance protein (GMP) EBNA1 (refs 4, 5). Indeed, EBNA1 is essential for EBV genome replication and maintenance and as such expressed in all dividing EBV-infected cells.…”

Epigenetics and Genetics of Viral Latency

“…These viruses encode a structurally-related sequence-specific DNA-binding protein that tethers the viral episome to the host metaphase chromosome during mitosis. EBV EBNA1 (Frappier, 2015), KSHV LANA (Ballestas and Kaye, 2011; Uppal et al, 2014), and HPV E2 (McBride, 2013) share this function. Each protein interacts with host metaphase chromatin through multiple, and distinct cellular targets, including AT-rich DNA for EBNA1, core histones H2A and H2B for LANA, and chromatin associated factors BRD4 and ChlR1 for E2.…”