Burnham Lorrie A, Jaishankar Dinesh, Thompson Jeffrey M, Jones Kevin S, Shukla Deepak, Tiwari Vaibhav
Department of Biology, California State University San Bernardino, CA, USA.
Departments of Ophthalmology and Visual Sciences, Bioengineering and Microbiology/Immunology, University of Illinois Chicago, IL, USA.
Front Microbiol. 2016 Jun 22;7:973. doi: 10.3389/fmicb.2016.00973. eCollection 2016.
Cationic liposomes are widely used to facilitate introduction of genetic material into target cells during transfection. This study describes a non-receptor mediated herpes simplex virus type-1 (HSV-1) entry into the Chinese hamster ovary (CHO-K1) cells that naturally lack glycoprotein D (gD)-receptors using a commercially available cationic liposome: lipofectamine. Presence of cell surface heparan sulfate (HS) increased the levels of viral entry indicating a potential role of HS in this mode of entry. Loss of viral entry in the presence of actin de-polymerizing or lysosomotropic agents suggests that this mode of entry results in the endocytosis of the lipofectamine-virus mixture. Enhancement of HSV-1 entry by liposomes was also demonstrated in vivo using a zebrafish embryo model that showed stronger infection in the eyes and other tissues. Our study provides novel insights into gD receptor independent viral entry pathways and can guide new strategies to enhance the delivery of viral gene therapy vectors or oncolytic viruses.
阳离子脂质体在转染过程中被广泛用于促进遗传物质导入靶细胞。本研究描述了一种非受体介导的1型单纯疱疹病毒（HSV-1）进入天然缺乏糖蛋白D（gD）受体的中国仓鼠卵巢（CHO-K1）细胞的过程，该过程使用市售阳离子脂质体：Lipofectamine。细胞表面硫酸乙酰肝素（HS）的存在增加了病毒进入水平，表明HS在这种进入模式中具有潜在作用。在存在肌动蛋白解聚剂或溶酶体促渗剂的情况下病毒进入减少，这表明这种进入模式导致了Lipofectamine-病毒混合物的内吞作用。使用斑马鱼胚胎模型在体内也证明了脂质体对HSV-1进入的增强作用，该模型显示眼睛和其他组织中的感染更强。我们的研究为不依赖gD受体的病毒进入途径提供了新见解，并可指导增强病毒基因治疗载体或溶瘤病毒递送的新策略。
