Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women
Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women
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上海女性宫颈上皮内瘤变HPV16基因变异及功能意义
DOI：
10.1002/jmv.25618
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发表时间：
2020
影响因子：
12.7
通讯作者：
Li Fang
中科院分区：
文献类型：
--
作者：
Zhao Junwei;Zhu Jiacheng;Guo Junhan;Zhu Tailin;Zhong Jixing;Liu Min;Ruan Yetian;Liao Shujie;Li Fang
人乳头瘤病毒（HPV）16基因突变常与HPV持续感染和宫颈上皮内瘤变（CIN）有关。然而，HPV 16突变的功能意义仍然知之甚少。145 LCR/E6/E7的HPV 16分离株扩增和测序，HPV 16整合状态进行检测。共发现89个SNPs（LCR 68个，E6 13个，E7 8个），其中11个为非同义突变（E6 8个，E7 3个）。与T相比，E6中的H85 Y和E120 D变体在高度鳞状上皮内病变（HSIL）组中显著减少，T是TATA结合蛋白的潜在结合位点，在LCR变体中最常见。与A1-3相比，A4（亚洲人）与HSIL风险增加相关（P = .009）。HPV 16 E7中的N29和E6中的H85/E120可能分别通过影响p53和Rb的相互作用而破坏p53和Rb的降解，从而在癌变过程中发挥关键作用。总之，本研究的结果为HPV 16相关宫颈病变/癌症提供了预防和治疗干预措施。
Human papillomavirus (HPV)16 gene mutation is usually associated with persistent HPV infection and cervical intraepithelial neoplasia (CIN). However, the functional implications of HPV16 mutations remain poorly understood.145 LCR/E6/E7 of the HPV16 isolates were amplified and sequenced, and HPV16 integration status was detected. In total, 89 SNPs (68 in the LCR, 13 in E6, 8 in E7) were discovered, 11 of which were nonsynonymous mutations (8 in E6, 3 in E7). The H85Y and E120D variants in E6 were significantly reduced in the high‐grade squamous intraepithelial lesion (HSIL) group compared to the T,” a potential binding site for TATA‐binding protein, is the most common in LCR variants. A4 (Asian) was associated with an increased risk of HSIL compared to A1–3(P = .009). The H85/E120 in E6 and N29 in HPV16 E7 might play a critical role in carcinogenesis by disrupting p53 and Rb degradation due to affecting their interaction, respectively. In a word, the findings in this study provide preventative and therapeutic interventions of HPV16 ‐related cervical lesions/cancer.