Biology and Medical Research Unit, National Centre for Energy, Nuclear Sciences and Techniques (CNESTEN), Rabat, Morocco; Laboratory of Virology Microbiology, Quality, Biotechnologies/Eco-Toxicology and Biodiversity (LVMQB/ETB), Faculty of Sciences and Techniques of Mohammedia (FSTM), University of Hassan II Casablanca, Morocco.
Faculty of Sciences, Moulay Ismail University, Meknès, Morocco.
Gene. 2020 Jul 15;747:144682. doi: 10.1016/j.gene.2020.144682. Epub 2020 Apr 15.
Human Papillomavirus 16 (HPV16) is the most oncogenic HPV and the most associated genotype with cervical cancer development and progression. Currently, all developed vaccines are targeting HPV16 and were designed based on the major L1 capsid protein. Thus, evaluation of the diversity of HPV16 L1 sequence, mainly in the antigenic regions, will be of a great interest to assess the efficacy of the prophylactic vaccines and to predict the impact of genetic variations in these regions on the vaccination-induced immunity. A total of 377 HPV16 L1 sequences, published in public domain GenBank database, from the Americas, Africa, Asia, and Europe were collected and assembled. A total of 626 mutation events affecting 83 distinct nucleotides into the five antigenic regions of L1 gene of HPV16 were reported, and most SNPs were located in DE (27.38%, 23/83) and FG (31%, 26/83) loops. Overall, 4 mutations were frequently found in HPV16 sequences: T176N and N181T in EF loop; A266T in the FG loop and T353P/I/N HI loop. Of particular interest, some SNPs are ubiquitous and were found in all populations whereas others were population specific and their presence was limited to one or 2 at the maximum. Association between mutations in the antigenic regions and ethnicity was also investigated and showed that mutations in BC and DE loops were present with no significant difference in sequences from Europe, Asia, America and Africa. However, most mutations in FG loop are reported in sequences from European cases and are less pronounced in cases from America and Asia, whereas mutations EF and HI loops prevail in Asian cases. These data highlight a high number of variant amino acid residues that could affect the vaccination-induced immunity and impact the effectiveness of the prophylactic vaccination to fight against HPV, warranting the need of further investigation for vaccines and natural history studies of HPV16.
人乳头瘤病毒 16（HPV16）是最具致癌性的 HPV 病毒，也是与宫颈癌发展和进展最相关的基因型。目前，所有已开发的疫苗都针对 HPV16，并基于主要的 L1 衣壳蛋白设计。因此，评估 HPV16 L1 序列的多样性，主要是在抗原区域，对于评估预防性疫苗的功效以及预测这些区域的遗传变异对疫苗诱导免疫的影响将非常有意义。从美洲、非洲、亚洲和欧洲的公共领域 GenBank 数据库中收集并组装了总共 377 个人乳头瘤病毒 16 L1 序列。报告了影响 HPV16 L1 基因 5 个抗原区域的 83 个不同核苷酸的 626 个突变事件，大多数 SNPs 位于 DE（27.38%，23/83）和 FG（31%，26/83）环中。总体而言，HPV16 序列中经常发现 4 种突变：EF 环中的 T176N 和 N181T；FG 环中的 A266T 和 HI 环中的 T353P/I/N。特别值得注意的是，一些 SNPs 是普遍存在的，存在于所有人群中，而另一些则是特定于人群的，其存在最多限于一个或两个。还研究了抗原区域突变与种族的关系，结果表明，BC 和 DE 环中的突变在欧洲、亚洲、美洲和非洲的序列中没有显著差异，但 FG 环中的大多数突变存在于欧洲病例的序列中，在美洲和亚洲病例中则不明显，而 EF 和 HI 环中的突变则在亚洲病例中更为普遍。这些数据突出了大量可能影响疫苗诱导免疫的变异氨基酸残基，并影响预防性疫苗对抗 HPV 的有效性，需要进一步研究疫苗和 HPV16 的自然史。
