Natural Variations in BRLF1 Promoter Contribute to the Elevated Reactivation Level of Epstein-Barr Virus in Endemic Areas of Nasopharyngeal Carcinoma
Autor: | Shao Yi Huang, Si Qi Dong, Fang Wang, Mu Jianbing, Jiang Bo Zhang, Tong-Min Wang, Wei Hua Jia, Xi Zhao Li, Yong Qiao He, Xiao Hui Zheng |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male China Epstein-Barr Virus Infections Herpesvirus 4 Human Research paper BRLF1 Variation Biology medicine.disease_cause BZLF1 General Biochemistry Genetics and Molecular Biology Virus Immediate-Early Proteins 03 medical and health sciences 0302 clinical medicine Genotype medicine Epstein-Barr virus Humans Risk factor Promoter Regions Genetic Gene Nasopharyngeal Carcinoma Haplotype Genetic Variation Promoter Nasopharyngeal Neoplasms General Medicine medicine.disease Reactivation Epstein–Barr virus 030104 developmental biology Nasopharyngeal carcinoma 030220 oncology & carcinogenesis Immunology Trans-Activators Female |
Zdroj: | EBioMedicine |
ISSN: | 2352-3964 |
Popis: | Background: Epstein-Barr virus (EBV) infection is a crucial risk factor for nasopharyngeal carcinoma (NPC), but the mechanism for its elevated activation level in NPC endemic areas remains unclear. This study aims to identify the EBV natural variations contributed to the different reactivation potential between NPC endemic and non-endemic areas. Methods: 1030 subjects were recruited in China, including 303 healthy individuals from two NPC non-endemic areas, 483 healthy people from three endemic areas and 244 NPC patients. Among which, saliva DNA samples from 244 participants were sequenced for the EBV immediate early (IE) genes of BRLF1 and BZLF1, their promoters were included; the rest 786 subjects were used for the validation of significant variations among three different populations. Haplotype and population structure analysis were conducted. Dual-luciferase assay was used to detect the promoter activity. Results: A total of 246 distinct variations were detected, 29 showed significant difference in the frequencies between healthy people from NPC endemic area and non-endemic area. Population structure analysis clustered EBV strains into 9 subgroups mostly in accordance with the geographical origin of samples. Interestingly, two EBV genotypes, Rp-V1 and Rp-V2, were identified according to the linkage relationship of the variations in BRLF1 promoter (Rp). Rp-V1 has higher frequency in NPC endemic areas than in non-endemic areas (52.38% vs 18.15%, P=2.07×10-14), and was associated with higher oral EBV DNA levels (adjusted OR=1.64, 95% CI=1.21-2.24, P=0.002), suggesting a more powerful activation ability of Rp-V1 than that of the wild type Rp-WT of the EBV strain; On the contrary, Rp-V2 has higher frequency in NPC non-endemic areas than in endemic areas (18.48% vs 0.38%, P=1.17×10-7), might represent a reduced activation potential of EBV. Further dual-luciferase assay showed Rp-V1 has higher promoter activity while compared with Rp-V2 (P |
Databáze: | OpenAIRE |
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