title: 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.
authors.affiliation: Department of Medical Microbiology, Qingdao University Medical College, Qingdao, China.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Medical Microbiology, Qingdao University Medical College, Qingdao, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Microbiology, Qingdao University Medical College, Qingdao, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shu
authors.affiliation: Department of Medical Microbiology, Qingdao University Medical College, Qingdao, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Medical Microbiology, Qingdao University Medical College, Qingdao, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Luo
mesh_terms: D002277:Carcinoma; D002681:China / Q000453:epidemiology; D019353:Endemic Diseases; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000453:epidemiology / Q000821:virology*; D014644:Genetic Variation; D005838:Genotype; D064368:Healthy Volunteers; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008223:Lymphoma / Q000453:epidemiology / Q000821:virology; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology / Q000821:virology*; D058974:Phylogeography; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000821:virology; D014763:Viral Matrix Proteins / Q000235:genetics*
chemical_list: C539239:BNLF21 protein, human herpesvirus 4; D014763:Viral Matrix Proteins
keywords: BNLF2a gene; Epstein-Barr virus; gastric carcinoma; lymphoma; nasopharyngeal carcinoma; polymorphism