Sequence analysis of EBV immune evasion gene BNLF2a in EBV associated tumors and healthy individuals from nasopharyngeal carcinoma endemic and non‐endemic regions of China

Abstract

BNLF2a is an Epstein-Barr virus (EBV) immune evasion gene. Its protein is located in the endoplasmic reticulum (ER) membrane, and can inhibit the antigen transporting function of TAP, thereby perturbing the immune response to EBV in lytic and prelatent phase. In order to explore whether the polymorphism of BNLF2a gene has a role in different types of EBV associated tumors, we conducted complete sequencing of the gene BNLF2a in 408 cases of EBV positive tumors (76 lymphomas, 45 gastric carcinomas, and 85 nasopharyngeal carcinomas in northern China and 27 lymphomas, 30 gastric carcinomas, and 57 nasopharyngeal carcinomas in southern China) and throat washings from healthy individuals (39 in northern China and 49 in southern China). Two main variant types of BNLF2a were identified. Type BNLF2a-A, which was similar to B95-8, was dominant in all sub-populations (66.7-100%) in this study. Type BNLF2a-B was characterized by the mutations at position 8 and 40. The variation patterns of BNLF2a were significantly different between samples from northern and southern China (P < 0.05), and between the tumors and healthy donor samples from the northern China (P < 0.0167). Type BNLF2a-B was more frequent in healthy donors of northern China (33.3%), and the proportion of this type was higher in the northern than in the southern NPCs. These data demonstrate that the BNLF2a gene is highly conserved, and its polymorphism is geographically restricted. Type BNLF2a-B is more prevalent in northern China and may be less tumor transformative.

SNHG8 is identified as a key regulator of epstein-barr virus(EBV)-associated gastric cancer by an integrative analysis of lncRNA and mRNA expression

“…The BNLF2a protein has two domains: a hydrophilic, cytosolic N-terminal domain and a hydrophobic, membrane-spanning C-terminal domain [30]. Both domains are required for immune escape, which involves the disruption of viral peptide transport into the endoplasmic reticulum and of peptide loading onto human leukocyte antigen class I molecules; this disruption leads to lower levels of endogenous antigen presentation, thus preventing recognition by CD8+ T-cells [30, 31]. …”

Camptothecin inhibits the progression of NPC by regulating TGF‑β‑induced activation of the PI3K/AKT signaling pathway

“…Notably, the results of the present study indicated that camptothecin regulated the viability of NPC cells by regulating TGF-β-induced activation of the PI3K/AKT signaling pathway. Increased incidence of NPC and increased mortality rates for patients with NPC have been reported in China (26)(27)(28).…”

Long non-coding RNAs in Epstein–Barr virus-related cancer

“…Furthermore, BHRF1 has 38% sequence homology with the antiapoptotic protein Bcl-2 and the function of BHLF is also similar to that of Bcl-2, leading to persistent virus infection and contributing to tumourigenesis [ 75 ]. Additionally, BNLF2a, an early gene, may contribute to immune escape because its protein has two domains(a hydrophilic, cytosolic N-terminal domain and a hydrophobic, membrane-spanning C-terminal domain) both of which are associated with the disruption of viral peptide transport into the endoplasmic reticulum and of peptide loading onto human leukocyte antigen class I molecules, leading to the reduction of endogenous antigen presentation and preventing recognition by CD8+ T-cells [ 76 , 77 ]. TRIM28, TRPM7 and NAP1L1 influence downstream cancer pathways in GC.…”