Programa de Doctorado en Ciencias Biomédicas, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Circuito Escolar S/N, Ciudad Universitaria, Delegación Coyoacán, 04500, Mexico City, Mexico.
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Av. San Fernando No. 22, Col. Sección XVI, Tlalpan, 14080, Mexico City, Mexico.
Sci Rep. 2019 Sep 20;9(1):13620. doi: 10.1038/s41598-019-49886-4.
The Human Papillomavirus (HPV) E1 protein is the only viral protein with enzymatic activity. The main known function of this protein is the regulation of the viral DNA replication. Nevertheless, it has been demonstrated that the ablation of HPV18 E1 mRNA in HeLa cells promotes a deregulation of several genes, particularly those involved in host defense mechanisms against viral infections; however, the specific contribution of E1 protein in HPV-independent context has not been studied. The aim of this work was to determine the effect of the HPV E1 protein in the regulation of cellular gene expression profiles evaluated through RNA-seq. We found that E1 proteins from HPV16 and 18 induced an overexpression of different set of genes associated with proliferation and differentiation processes, as well as downregulation of immune response genes, including IFNβ1 and IFNλ1 and Interferon-stimulated gene (ISG), which are important components involved in the antiviral immune response. Together, our results indicate that HR-(High-Risk) and LR-(Low-Risk) HPV E1 proteins play an important role in inhibiting the anti-viral immune response.
人乳头瘤病毒（HPV）E1 蛋白是唯一具有酶活性的病毒蛋白。该蛋白的主要已知功能是调节病毒 DNA 复制。然而，已经证明在 HeLa 细胞中 HPV18 E1 mRNA 的缺失会促进几个基因的失调，特别是那些参与宿主抗病毒感染防御机制的基因；然而，尚未研究 E1 蛋白在 HPV 非依赖性背景下的特定贡献。这项工作的目的是确定 HPV E1 蛋白在通过 RNA-seq 评估的细胞基因表达谱调节中的作用。我们发现 HPV16 和 18 的 E1 蛋白诱导与增殖和分化过程相关的不同基因集的过表达，以及免疫反应基因的下调，包括 IFNβ1 和 IFNλ1 和干扰素刺激基因（ISG），它们是参与抗病毒免疫反应的重要组成部分。总之，我们的结果表明 HR-（高危型）和 LR-（低危型）HPV E1 蛋白在抑制抗病毒免疫反应中发挥重要作用。
