Bello-Morales Raquel, Crespillo Antonio Jesús, Praena Beatriz, Tabarés Enrique, Revilla Yolanda, García Elena, Fraile-Ramos Alberto, Baron Wia, Krummenacher Claude, López-Guerrero José Antonio
Universidad Autónoma de Madrid, Departamento de Biología Molecular, Edificio de Biología, Darwin 2, Cantoblanco, 28049, Madrid, Spain.
Universidad Complutense de Madrid, Facultad de Medicina, Plaza de Ramón y Cajal, s/n Ciudad Universitaria, 28040, Madrid, Spain.
PLoS One. 2016 Jan 25;11(1):e0147885. doi: 10.1371/journal.pone.0147885. eCollection 2016.
Herpes simplex virus type 1 (HSV-1) has the ability to enter many different hosts and cell types by several strategies. This highly prevalent alphaherpesvirus can enter target cells using different receptors and different pathways: fusion at a neutral pH, low-pH-dependent and low-pH-independent endocytosis. Several cell receptors for viral entry have been described, but several observations suggest that more receptors for HSV-1 might exist. In this work, we propose a novel role for the proteolipid protein (PLP) in HSV-1 entry into the human oligodendrocytic cell line HOG. Cells transfected with PLP-EGFP showed an increase in susceptibility to HSV-1. Furthermore, the infection of HOG and HOG-PLP transfected cells with the R120vGF virus--unable to replicate in ICP4-defficient cells--showed an increase in viral signal in HOG-PLP, suggesting a PLP involvement in viral entry. In addition, a mouse monoclonal antibody against PLP drastically inhibited HSV-1 entry into HOG cells. PLP and virions colocalized in confocal immunofluorescence images, and in electron microscopy images, which suggest that PLP acts at the site of entry into HOG cells. Taken together these results suggest that PLP may be involved in HSV-1 entry in human oligodendrocytic cells.
1型单纯疱疹病毒(HSV-1)能够通过多种策略进入许多不同的宿主和细胞类型。这种高度流行的α疱疹病毒可以利用不同的受体和不同的途径进入靶细胞:在中性pH下融合、低pH依赖性和低pH非依赖性内吞作用。已经描述了几种用于病毒进入的细胞受体,但一些观察结果表明可能存在更多的HSV-1受体。在这项研究中,我们提出了蛋白脂质蛋白(PLP)在HSV-1进入人少突胶质细胞系HOG中的新作用。用PLP-EGFP转染的细胞对HSV-1的易感性增加。此外,用R120vGF病毒感染HOG和HOG-PLP转染细胞(该病毒在ICP4缺陷细胞中无法复制),结果显示HOG-PLP中的病毒信号增加,这表明PLP参与了病毒进入过程。此外,一种抗PLP的小鼠单克隆抗体可显著抑制HSV-1进入HOG细胞。在共聚焦免疫荧光图像和电子显微镜图像中,PLP与病毒粒子共定位,这表明PLP在进入HOG细胞的部位起作用。综合这些结果表明,PLP可能参与了HSV-1进入人少突胶质细胞的过程。