Aksoy Pınar, Meneses Patricio I
Department of Biological Sciences, Fordham University, Bronx, New York, United States of America.
PLoS One. 2017 Jan 17;12(1):e0170158. doi: 10.1371/journal.pone.0170158. eCollection 2017.
Persistent infection with high-risk human papillomavirus (HPV) genotype is a major factor leading to many human cancers. Mechanisms of HPV entry into host cells and genome trafficking towards the nucleus are incompletely understood. Dopachrome tautomerase (DCT) was identified as a cellular gene required for HPV infection in HeLa cells on a siRNA screen study. Here, we confirm that DCT knockdown significantly decreases HPV infection in the human keratinocyte HaCaT cells as was observed in HeLas. We investigated the effects of DCT knockdown and found that DCT depletion caused increased reactive oxygen species (ROS) levels, DNA damage and altered cell cycle in HaCaT cells. We observed increased viral DNA localization at the endoplasmic reticulum but an overall decrease in infection in DCT knockdown cells. This observation suggests that viral DNA might be retained in the ER due to altered cell cycle, and viral particles are incapable of further movement towards the nucleus in DCT knockdown cells.
高危型人乳头瘤病毒（HPV）基因型的持续感染是导致多种人类癌症的主要因素。HPV进入宿主细胞以及基因组向细胞核运输的机制尚未完全明确。在一项RNA干扰筛选研究中，多巴色素互变异构酶（DCT）被确定为HeLa细胞中HPV感染所需的一种细胞基因。在此，我们证实，正如在HeLa细胞中所观察到的那样，DCT基因敲低显著降低了人角质形成细胞HaCaT中的HPV感染。我们研究了DCT基因敲低的影响，发现DCT缺失导致HaCaT细胞中的活性氧（ROS）水平升高、DNA损伤以及细胞周期改变。我们观察到内质网上病毒DNA定位增加，但DCT基因敲低细胞中的感染总体减少。这一观察结果表明，由于细胞周期改变，病毒DNA可能保留在内质网中，并且在DCT基因敲低细胞中病毒颗粒无法进一步向细胞核移动。
