EBV and Lymphomagenesis

Abstract

The clinical significance of Epstein–Barr virus (EBV) cannot be understated. Not only does it infect approximately 90% of the world’s population, but it is also associated with numerous pathologies. Diseases linked to this virus include hematologic malignancies such as diffuse large B-cell lymphoma, Hodgkin lymphoma, Burkitt lymphoma, primary CNS lymphoma, and NK/T-cell lymphoma, epithelial malignancies such as nasopharyngeal carcinoma and gastric cancer, autoimmune diseases such as multiple sclerosis, Graves’ disease, and lupus. While treatment for these disease states is ever evolving, much work remains to more fully elucidate the relationship between EBV, its associated disease states, and their treatments. This paper begins with an overview of EBV latency and latency-associated proteins. It will then review EBV’s contributions to select hematologic malignancies with a focus on the contribution of latent proteins as well as their associated management.

The biology and treatment of Epstein-Barr virus-positive diffuse large B cell lymphoma, NOS

“…The proportion of EBV positive rate in DLBCL is relatively higher (8.7%–11.4%) in Asia and Latin America than in Western countries (<5%) [ 4 ]. EBV infection was a risk factor for lymphomagenesis, such as Burkitt lymphoma, NK/T cell lymphoma and EBV+DLBCL-NOS [ 18 , 19 ]. The incidence of EBV+DLBCL-NOS in China accounts for 3.8%–19.0% of DLBCL, and is more common in southern China [ 20 , 21 ].…”

Mechanisms of T cell evasion by Epstein-Barr virus and implications for tumor survival

“…B cell EBV nuclear antigen 1 (EBNA1) is expressed in all latent phases except latency 0 ( 77 , 78 ). It has important functions with regards to replication of the EBV plasmid genome.…”

“…EBV nuclear antigen 2 (EBNA2) is expressed during latency III ( 78 ). As one of the first genes expressed during infection ( 84 ), it is essential in early latent gene reprogramming ( 85 ).…”

“…EBV Nuclear Antigen 3 proteins A (EBNA3A), B (EBNA3B), and C (EBNA3C) are expressed during latency III ( 77 , 78 ). There have been numerous studies using stop codons inserted into the open reading frames of EBNA3A, EBNA3B, and EBNA3C that have shown EBNA3A and EBNA3C are necessary for transformation of EBV-infected B cells ( 91 , 92 ), although EBNA3B is not ( 93 ).…”

IFIT3 inhibits Epstein‐Barr virus reactivation via upregulating innate immunity

“…Epstein‐Barr virus (EBV), also known as human herpesvirus type 4, has a double‐stranded DNA genome of more than 170 kb 1 . It is also the first DNA virus confirmed to be associated with human tumors of lymphatic and epithelial origin, such as Burkitt's lymphoma 2 and nasopharyngeal carcinoma (NPC) 3 . EBV infection status includes latent infection and lytic replication 4 .…”