Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women. Issue 3 (18th November 2019)

• Record Type: Journal Article
• Authors: Zhao, Junwei; Zhu, Jiacheng; Guo, Junhan; Zhu, Tailin; Zhong, Jixing; Liu, Min; Ruan, Yetian; Liao, Shujie; Li, Fang
• Is Part Of: Journal of medical virology. Volume 92:Issue 3(2020)
• Page Start: 372
• Page End: 381
• Publication Date: 2019-11-18
• Subjects: cervical intraepithelial neoplasia -- HPV16 E6/E7/LCR -- phylogenetic analysis -- structural analysis -- variant; Virology -- Periodicals; 616
• DOI: 10.1002/jmv.25618
• Languages: English
• ISSNs: 0146-6615

Abstract

Abstract: 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 <HSIL group ( P = .046 and .005), conversely the N29S in E7( P = .01). Amino acid substitutions (D32N/E, E36Q, H85Y, and E120D in E6 and N29H/S and R77C in E7) were predicted to have an effect on conserved structural and functional residues, and five amino acid substitutions (H85Y, E36Q, I34L, and D32E in E6; R77C in E7) would potentially change the secondary structure. "6329G>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. Highlight: The variants analysis of HPV16 E6, E7 and LCR gene from clinical samples, try reconstructing the phylogenetic relationship of the mutation and understand the effect of variants on carcinogenesis. 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.