El-Aliani Aissam, Alaoui My Abdelaziz El, Chaoui Imane, Ennaji My Mustapha, Attaleb Mohammed, Mzibri Mohammed El
Unit of Biology and Medical Research, National Centre Natuional de l´Energie, des Sciences et des techniques Nucléaires. Morocco.
Laboratory of Virology Microbiology, Quality, Biotechnologies/Eco-Toxicology and Biodiversity (LVMQB/ETB), Faculté des Sciences et Techniques Mohammedia, Morocco.
Bioinformation. 2017 Aug 31;13(8):241-248. doi: 10.6026/97320630013241. eCollection 2017.
HPV L1 protein is a corner stone in HPV structure, it's involved in the formation of the viral capsid; widely used as a systematic material and considered as the main component in vaccines development and production. The present study aims to characterize genetic variation of L1 gene of HPV 16 specimens and to evaluate in silico the impact of major variants on the epitope change affecting its conformational structure. A fragment of L1 gene from 35 HPV 16 confirmed specimens were amplified by PCR and sequenced. Overall, five amino acids residues changes were reported: T390P in 16 specimens, M425I and M431I in 2 cases, insertion of Serine at 460 and aspartic acid deletion at position 477 in all analyzed cases. The 3D generated model showed that T389P amino acid substitution is located in the H-I loop; the two substitutions M424I and M430I are both located in the H2 helice. The Serine insertion and aspartic acid deletion are located in the H4 helice and B-C loop, respectively. Superimposition of sequences' structures showed that they share a very similar conformation highlighting that the reported amino acids variations don't affect the structure of the L1 protein. However T389P, located in the H-I loop identified as an immunogenetic region of L1 capsid, was reported in 51.4% of cases could interact with vaccines induced monoclonal antibodies suggesting a potential impact on the efficacy of available anti-HPV vaccines.
人乳头瘤病毒1型L1蛋白是人乳头瘤病毒结构的基石，参与病毒衣壳的形成；广泛用作系统性材料，并被视为疫苗研发和生产的主要成分。本研究旨在表征人乳头瘤病毒16型标本L1基因的遗传变异，并通过计算机模拟评估主要变异对影响其构象结构的表位变化的影响。通过聚合酶链反应扩增并测序了35例确诊为人乳头瘤病毒16型标本的L1基因片段。总体而言，报告了五个氨基酸残基变化：16个标本中出现T390P，2例中出现M425I和M431I，所有分析病例中在460位插入丝氨酸，在477位缺失天冬氨酸。生成的三维模型显示，T389P氨基酸取代位于H-I环；M424I和M430I这两个取代均位于H2螺旋。丝氨酸插入和天冬氨酸缺失分别位于H4螺旋和B-C环。序列结构的叠加显示它们具有非常相似的构象，突出表明报告的氨基酸变异不影响L1蛋白的结构。然而，位于被确定为L1衣壳免疫遗传区域的H-I环中的T389P，在51.4%的病例中被报告可与疫苗诱导的单克隆抗体相互作用，提示可能对现有抗人乳头瘤病毒疫苗的疗效产生影响。
