Vieira Alves Melina, Oliveira Pereira Guilherme, Alves Dos Santos Silva Letícia, Dória Araújo Edilaine, Barreto da Silva Brenda Evenlin, Dolce de Lemos Lígia Mara, de Aragão Batista Marcus Vinicius
Laboratory of Molecular Genetics and Biotechnology (GMBio), Department of Biology, Center for Biological and Health Sciences, Federal University of Sergipe, São Cristóvão, SE, 49107-230, Brazil.
Graduate Program in Health Sciences, Federal University of Sergipe, Aracaju, SE, 49060-108, Brazil.
J Med Microbiol. 2025 Mar;74(3). doi: 10.1099/jmm.0.001981.
The human papillomavirus (HPV) is one of the main oncogenic viruses. High-risk HPV types are associated with the development of cervical cancers. In addition, it is known that some mutations in HPV genes, or variant viral lineages, have been associated with greater oncogenic risk. The L1 protein is the major component of the viral capsid and is therefore used in currently available vaccines. However, the characterization of mutations in the L1 gene, which is relevant to increasing the knowledge of the immune escape mechanisms used by the virus, is still incipient. This study aimed to characterize mutations associated with antigenic domains in the L1 protein of HPVs isolated from cervical samples of women living with HIV in Northeastern Brazil. L1 gene sequences were obtained from the samples, and the mutations and the viral variants were characterized. Phylogenetic and functional analyses of the structure of the L1 protein were carried out. A total of 41 HPV variant isolates were obtained, distributed among 16 different viral types. Of this, 25 non-synonymous mutations were evaluated regarding the stability of the L1 protein. It was observed that 10 of these mutations were predicted to increase, and 14 to decrease, the stability of the L1 protein and that most of them occurred in the FG hypervariable antigenic loop. These results add useful knowledge to understanding the biological and immunological aspects of HPV variants and the impact of these mutations on the development of vaccine strategies.
人乳头瘤病毒(HPV)是主要的致癌病毒之一。高危型HPV与宫颈癌的发生有关。此外,已知HPV基因中的一些突变或病毒变异谱系与更高的致癌风险相关。L1蛋白是病毒衣壳的主要成分,因此被用于目前可用的疫苗中。然而,L1基因突变的特征描述仍处于初期阶段,这对于增加对病毒所使用的免疫逃逸机制的了解具有重要意义。本研究旨在对从巴西东北部感染HIV的女性宫颈样本中分离出的HPV的L1蛋白中与抗原结构域相关的突变进行特征描述。从样本中获取L1基因序列,并对突变和病毒变异进行特征分析。对L1蛋白的结构进行了系统发育和功能分析。共获得41株HPV变异分离株,分布在16种不同的病毒类型中。其中,对25个非同义突变进行了L1蛋白稳定性评估。结果发现,其中10个突变预计会增加L1蛋白的稳定性,14个会降低其稳定性,且大多数突变发生在FG高变抗原环中。这些结果为理解HPV变异的生物学和免疫学方面以及这些突变对疫苗策略开发的影响增添了有用的知识。