机构：[1]Institute of Medical Biology, Chinese Academy of Medical Sciences, andPeking Union Medical College, Kunming 650118, People’s Republic of China[2]Yunnan Key Laboratory of Vaccine Research and Development on SevereInfectious Diseases, Kunming 650118, People’s Republic of China[3]YunnanProvincial Key Laboratory of Vector-borne Diseases Control and Research,Pu’er 665000, People’s Republic of China[4]The First Affiliated Hospital ofKunming Medical University, Kunming 650032, People’s Republic of China昆明医科大学附属第一医院[5]The Third Affiliated Hospital of Kunming Medical University, YunnanProvincial Tumor Hospital, Kunming 650118, People’s Republic of China外科科室肿瘤科昆明医科大学附属第一医院[6]Kunming Medical University, Kunming 650500, People’s Republic of China[7]Institute of Pediatric Disease Research in Yunnan, the Affiliated Children’sHospital of Kunming Medical University, Kunming 650228, People’s Republicof China
Backgroud: Variations in HPV LCR/E6/E7 have been shown to be associated with the viral persistence and cervical cancer development. So far, there are few reports about the polymorphisms of the HPV-58 LCR/E6/E7 sequences in Southwest China. This study aims to characterize the gene polymorphisms of the HPV-58 LCR/E6/E7 sequences in women of Southwest China, and assess the effects of variations on the immune recognition of viral E6 and E7 antigens. Methods: Twelve LCR/E6/E7 of the HPV-58 isolates were amplified and sequenced. A neighbor-joining phylogenetic tree was constructed by MEGA 7.0, followed by the secondary structure prediction of the related proteins using PSIPRED v3.3. The selection pressure acting on the HPV-58 E6 and E7 coding regions was estimated by Bayes empirical Bayes analysis of PAML 4.8. Meanwhile, the MHC class-I and II binding peptides were predicted by the ProPred-I server and ProPred server. The transcription factor binding sites in the HPV-58 LCR were analyzed using the JASPAR database. Results: Twenty nine SNPs (20 in the LCR, 3 in the E6, 6 in the E7) were identified at 27 nucleotide sites across the HPV58 LCR/E6/E7. From the most variable to the least variable, the nucleotide variations were LCR > E7 > E6. The combinations of all the SNPs resulted in 11 unique sequences, which were clustered into the A lineage (7 belong to A1, 2 belong to A2, and 2 belong to A3). An insertion (TGTCAGTTTCCT) was found between the nucleotide sites 7280 and 7281 in 2 variants, and a deletion (TTTAT) was found between 7429 and 7433 in 1 variant. The most common nonsynonymous substitution V77A in the E7 was observed in the sequences encoding the a-helix. 63G in the E7 was determined to be the only one positively selected site in the HPV-58 E6/E7 sequences. Six non-synonymous amino acid substitutions (including S71F and K93 N in the E6, and T20I, G41R, G63S/D, and V77A in the E7) were affecting multiple putative epitopes for both CD4(+) and CD8(+) T-cells. In the LCR, C7265G and C7266T were the most variable sites and were the potential binding sites for the transcription factor SOX10. Conclusion: These results provide an insight into the intrinsic geographical relatedness and biological differences of the HPV-58 variants, and contribute to further research on the HPV-58 epidemiology, carcinogenesis, and therapeutic vaccine development.
基金：
CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-3-026]; National "Twelfth Five Year" "major new drug discovery" technology major projects [2012ZX09104-302]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81171946]; Natural Science Foundation of Yunnan ProvinceNatural Science Foundation of Yunnan Province [2016FA029]; Jointly Supported Foundation of the National Project in Yunnan Province [2013GA018]
第一作者机构：[1]Institute of Medical Biology, Chinese Academy of Medical Sciences, andPeking Union Medical College, Kunming 650118, People’s Republic of China[2]Yunnan Key Laboratory of Vaccine Research and Development on SevereInfectious Diseases, Kunming 650118, People’s Republic of China[3]YunnanProvincial Key Laboratory of Vector-borne Diseases Control and Research,Pu’er 665000, People’s Republic of China
通讯作者：
推荐引用方式(GB/T 7714)：
Xi Juemin,Chen Junying,Xu Miaoling,et al.The polymorphisms of LCR, E6, and E7 of HPV-58 isolates in Yunnan, Southwest China[J].VIROLOGY JOURNAL.2018,15:doi:10.1186/s12985-018-0986-7.
APA：
Xi, Juemin,Chen, Junying,Xu, Miaoling,Yang, Hongying,Wen, Songjiao...&Sun, Qiangming.(2018).The polymorphisms of LCR, E6, and E7 of HPV-58 isolates in Yunnan, Southwest China.VIROLOGY JOURNAL,15,
MLA：
Xi, Juemin,et al."The polymorphisms of LCR, E6, and E7 of HPV-58 isolates in Yunnan, Southwest China".VIROLOGY JOURNAL 15.(2018)
