Mobini Kesheh Mina, Barazandeh Mohadeseh, Kaffashi Amir, Shahkarami Mohammad Kazem, Nadji Seyed Alireza
Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Microbiology Department, Qom Islamic Azad University, Qom, Iran.
Can J Infect Dis Med Microbiol. 2022 Jan 25;2022:4759871. doi: 10.1155/2022/4759871. eCollection 2022.
Human papillomavirus HPV) 16 and HPV 18 account for 75% of all cervical cancers. The L1 gene, encoding the major surface protein (MSP), is used to classify HPV types (lineages and sublineages), genotypes, and intratypic variants. Therefore, this study aimed to investigate the lineages, sublineages, genetic variabilities, and mutation effects on transcription factor binding sites by using partial sequences of the HPV 16 and HPV 18 long control regions (LCRs) in these samples.
After DNA isolation from 56 positive samples, the LCR of HPV 16 and HPV 18 were amplified using specific primers, and phylogenetic trees were drawn through MEGA X. Compared to the reference sequences, single nucleotide polymorphisms (SNPs) were identified. The transcription binding sites were also evaluated using the online PROMO database.
The LCRs of 52 samples were successfully sequenced. Overall, 81.58% of all HPV 16 variants belonged to the D1 sublineage, followed by A4 (13.16%), A1 (2.63%), and C1 (2.63%) sublineages. All HPV 18 isolates belonged to A sublineage, 92.85% to A3 sublineage, and 7.15% to A4 sublineage. Out of 27 SNPs in the HPV 16 LCR, A7382T, T7384G, C7387T, C7393G, A7431G, T7448C, and C7783A were HPV 16-specific. Also, among 14 SNPs in the HPV 18 LCR, C7577A and A7943T were not previously reported. An insertion (C) between 7432 and 7433 positions was identified in all studied HPV 16 variants. Besides, most of the HPV 16 mutations were embedded in the YY1, TFIID, Oct-2, and NF-1 binding sites, while c-Fos and MBF1, as the most common binding sites, were affected by HPV 18 LCR mutations.
The present results showed that D1 and A3 were the dominant sublineages of HPV 16 and HPV 18, respectively. Therefore, women infected with these variants need to be examined in further longitudinal studies to obtain more information about the oncogenic potential of these dominant variants in Iran. Besides, YY1, TFIID, Oct-2, NF-1, c-Fos, and MBF1 were the most frequent binding sites, which were influenced by the mutations.
人乳头瘤病毒（HPV）16型和HPV 18型导致了75%的宫颈癌。编码主要表面蛋白（MSP）的L1基因用于对HPV类型（谱系和亚谱系）、基因型和型内变异进行分类。因此，本研究旨在通过使用这些样本中HPV 16型和HPV 18型长控制区（LCR）的部分序列，研究其谱系、亚谱系、遗传变异性以及对转录因子结合位点的突变影响。
从56份阳性样本中提取DNA后，使用特异性引物扩增HPV 16型和HPV 18型的LCR，并通过MEGA X绘制系统发育树。与参考序列相比，鉴定出单核苷酸多态性（SNP）。还使用在线PROMO数据库评估转录结合位点。
成功对52个样本的LCR进行了测序。总体而言，所有HPV 16型变体中81.58%属于D1亚谱系，其次是A4（13.16%）、A1（2.63%）和C1（2.63%）亚谱系。所有HPV 18型分离株均属于A亚谱系，92.85%属于A3亚谱系，7.15%属于A4亚谱系。在HPV 16型LCR的27个SNP中，A7382T、T7384G、C7387T、C7393G、A7431G、T7448C和C7783A是HPV 16型特异性的。此外，在HPV 18型LCR的14个SNP中，C7577A和A7943T此前未被报道。在所有研究的HPV 16型变体中，在7432和7433位之间鉴定出一个插入（C）。此外，大多数HPV 16型突变嵌入YY1、TFIID、Oct-2和NF-1结合位点，而c-Fos和MBF1作为最常见的结合位点，受到HPV 18型LCR突变的影响。
目前的结果表明，D1和A3分别是HPV 16型和HPV 18型的主要亚谱系。因此，感染这些变体的女性需要在进一步的纵向研究中进行检查，以获取更多关于伊朗这些主要变体致癌潜力的信息。此外，YY1、TFIID、Oct-2、NF-1、c-Fos和MBF1是最常见的结合位点，受到突变的影响。
