四川地区受威胁的α-9型人乳头瘤病毒中HPV-35 E6 E7的多态性分析与治疗疫苗靶表位筛选

IF 4 3区 医学 Q2 VIROLOGY
Jiaoyu He, Tianjun Li, Chunlan Cheng, Ning Li, Peng Gao, Dan Lei, Rong Liang, Xianping Ding
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Among the 406 HPV-positive samples, 31 HPV-35 were detected, 24 HPV-35 E6 and 26 E7 were successfully amplified and sequenced, five nucleotide mutations in E6 and three in E7 were detected, T232C, T434G of E6 (W78R, I145R) and C67T, G84T of E7 (H23Y, L28F) were non-synonymy mutation. PAML 4.8 server was used to detect positive selection sites of HPV-35 E6, E7, and E6 is W78R. Phyre2 were used to predict and analyze protein structures, W78R made influences on protein structure. IEDB were used to screen epitopes vaccine target for HPV-35 affection therapy, and 5 HPV-35 E6 and 3 HPV-35 E7 most potential epitopes were obtained, the most potential peptides for therapy vaccine design were 79-91YRYSVYGETLEKQ, 45-60FACYDLCIVREGQPY, 124-135RFHNIGGRWTGR of E6; 3-19GEITTLQDYVLDLEPEA, 38-47TIDGPAGQAK, 70-88VQSTHIDIRKLEDLLMGTF of E7 and W78R mainly decreased the epitopes affinity. 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引用次数: 0

摘要

高危人乳头瘤病毒(HR-HPV)持续感染与宫颈癌和鳞状上皮内病变(SIL)的发生密切相关。在四川,以HR-HPV型为主的α-9型HPV占HR-HPV感染的75%。HPV的肿瘤蛋白E6和E7在肿瘤的发生和发展中起着至关重要的作用。值得注意的是,HPV-35 是 α-9 属中唯一未被纳入九价 HPV 预防性疫苗的 HR-HPV 类型。我们采集了四川的宫颈细胞样本,用于检测 HPV 和进行基因分型。在406份HPV阳性样本中,检测到31个HPV-35,成功扩增并测序了24个HPV-35 E6和26个E7,检测到E6中的5个核苷酸突变和E7中的3个核苷酸突变,其中E6中的T232C、T434G(W78R、I145R)和E7中的C67T、G84T(H23Y、L28F)为非同义突变。利用 PAML 4.8 服务器检测了 HPV-35 E6、E7 的正选择位点,其中 E6 为 W78R。利用 Phyre2 预测和分析蛋白质结构,W78R 对蛋白质结构有影响。利用 IEDB 筛选 HPV-35 亲和素治疗疫苗靶标表位,获得了 5 个 HPV-35 E6 和 3 个 HPV-35 E7 最有潜力的表位,其中最有潜力的治疗疫苗设计肽是 E6 的 79-91YRYSVYGETLEKQ、45-60FACYDLCIVREGQPY、124-135RFHNIGGRWTGR;E7的 3-19GEITTLQDYVLDLEPEA、38-47TIDGPAGQAK、70-88VQSTHIDIRKLEDLLMGTF 和 W78R 主要降低了表位亲和力。结论 研究发现,HPV-35 E6 和 E7 基因正选择位点的氨基酸取代会影响蛋白质结构,并降低抗原表位的总体亲和力。这一观察结果与阳性选择位点的进化意义相吻合,阳性选择位点可能赋予病毒优势,使受感染细胞更难被免疫系统检测到,从而增强 HPV 对宿主环境的适应性。对HPV-35 E6、E7的多态性分析有助于丰富四川地区α-9型HPV的数据,对提高临床检测的有效性大有裨益。此外,这些发现还为HPV相关疾病的防治提供了相关理论基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The polymorphism analysis and therapy vaccine target epitopes screening of HPV-35 E6 E7 among the threaten α-9 HPV in Sichuan area
High-risk human papilloma virus (HR-HPV) persistent infection is closely associated with the development of cervical cancer and squamous intraepithelial lesion (SIL).The α-9 HPVs, which is predominantly composed of HR-HPV types, account for 75% of HR-HPV infection in Sichuan. The oncoproteins E6 and E7 of HPV play a crucial role in tumor initiation and progression. Notably, HPV-35 is the only HR-HPV type within the α-9 genus that is not included in the nine-valent HPV prophylactic vaccine. Cervical cell samples obtained from Sichuan were collected for HPV detection and genotyping. Among the 406 HPV-positive samples, 31 HPV-35 were detected, 24 HPV-35 E6 and 26 E7 were successfully amplified and sequenced, five nucleotide mutations in E6 and three in E7 were detected, T232C, T434G of E6 (W78R, I145R) and C67T, G84T of E7 (H23Y, L28F) were non-synonymy mutation. PAML 4.8 server was used to detect positive selection sites of HPV-35 E6, E7, and E6 is W78R. Phyre2 were used to predict and analyze protein structures, W78R made influences on protein structure. IEDB were used to screen epitopes vaccine target for HPV-35 affection therapy, and 5 HPV-35 E6 and 3 HPV-35 E7 most potential epitopes were obtained, the most potential peptides for therapy vaccine design were 79-91YRYSVYGETLEKQ, 45-60FACYDLCIVREGQPY, 124-135RFHNIGGRWTGR of E6; 3-19GEITTLQDYVLDLEPEA, 38-47TIDGPAGQAK, 70-88VQSTHIDIRKLEDLLMGTF of E7 and W78R mainly decreased the epitopes affinity. Conclusions Amino acid substitution in the positive selection sites of HPV-35 E6 and E7 genes have been found to influence protein structure and to decrease the overall affinity of antigen epitopes. This observation aligns with the evolutionary significance of positive selection site, which may confer advantages to the virus by making infected cells more challenging for the immune system to detect, thereby enhancing HPV’s adaptability to the host environment. The polymorphism analysis of HPV-35 E6, E7 contributes to the enrichment of α-9 HPV data in Sichuan China, which is instrumental in improving the effectiveness of clinical detection. Furthermore, these findings provide a relevant theoretical foundation for the prevention and treatment of HPV-related diseases.
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来源期刊
Virology Journal
Virology Journal 医学-病毒学
CiteScore
7.40
自引率
2.10%
发文量
186
审稿时长
1 months
期刊介绍: Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies. The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.
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