da Silva-Júnior Antônio Humberto P, de Oliveira Silva Ruany Cristyne, Gurgel Ana Pavla A Diniz, Barros-Júnior Marconi Rêgo, Nascimento Kamylla Conceição Gomes, Santos Daffany Luana, Pena Lindomar J, Lima Rita de Cássia Pereira, Batista Marcus Vinicius de Aragão, Chagas Bárbara Simas, Freitas Antonio Carlos de
Laboratory of Molecular Studies and Experimental Therapy (LEMTE), Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Pernambuco, Brazil.
Department of Engineering and Environment, Federal University of Paraiba, João Pessoa 58033-455, Paraíba, Brazil.
Trop Med Infect Dis. 2024 Jun 26;9(7):140. doi: 10.3390/tropicalmed9070140.
The persistence of the human papillomavirus type 16 (HPV16) infection on the cervical epithelium contributes to the progression of cervical cancer. Studies have demonstrated that HPV16 genetic variants may be associated with different risks of developing cervical cancer. However, the E5 oncoprotein of HPV16, which is related to several cellular mechanisms in the initial phases of the infection and thus contributes to carcinogenesis, is still little studied. Here we investigate the HPV16 E5 oncogene variants to assess the effects of different mutations on the biological function of the E5 protein. We detected and analyzed the HPV16 E5 oncogene polymorphisms and their phylogenetic relationships. After that, we proposed a tertiary structure analysis of the protein variants, preferential codon usage, and functional activity of the HPV16 E5 protein. Intra-type variants were grouped in the lineages A and D using in silico analysis. The mutations in E5 were located in the T-cell epitopes region. We therefore analyzed the interference of the HPV16 E5 protein in the NF-kB pathway. Our results showed that the variants HPV16E5_49PE and HPV16E5_85PE did not increase the potential of the pathway activation capacity. This study provides additional knowledge about the mechanisms of dispersion of the HPV16 E5 variants, providing evidence that these variants may be relevant to the modulation of the NF-κB signaling pathway.
人乳头瘤病毒16型（HPV16）在宫颈上皮细胞中的持续感染会促使宫颈癌进展。研究表明，HPV16基因变异可能与宫颈癌发生的不同风险相关。然而，HPV16的E5癌蛋白在感染初期与多种细胞机制相关，从而促进致癌作用，但对其研究仍较少。在此，我们研究HPV16 E5癌基因变异，以评估不同突变对E5蛋白生物学功能的影响。我们检测并分析了HPV16 E5癌基因多态性及其系统发育关系。之后，我们对蛋白变异体进行了三级结构分析、HPV16 E5蛋白的偏好密码子使用情况及功能活性分析。通过计算机分析，同一类型内的变异体被分为A和D两个谱系。E5中的突变位于T细胞表位区域。因此，我们分析了HPV16 E5蛋白对NF-κB信号通路的干扰作用。我们的结果显示，变异体HPV16E5_49PE和HPV16E5_85PE并未增加该信号通路的激活能力。本研究提供了关于HPV16 E5变异体传播机制的更多知识，证明这些变异体可能与NF-κB信号通路的调节相关。
