Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, IL 60612, USA.
Antiviral Res. 2012 Dec;96(3):363-75. doi: 10.1016/j.antiviral.2012.09.020. Epub 2012 Oct 6.
The attachment of Herpes simplex virus type-2 (HSV-2) to a target cell requires ionic interactions between negatively charged cell surface co-receptor heparan sulfate (HS) and positively charged residues on viral envelop glycoproteins, gB and gC. Effective blocking of this first step of HSV-2 pathogenesis demonstrates significant prophylactic effects against the viral disease; any in vitro therapeutic effects of blocking this interaction, however, are not clear. Here, we provide new evidence that zinc oxide tetrapod micro-nanostructures synthesized by flame transport approach significantly block HSV-2 entry into target cells and, in addition, demonstrate the potential to stop the spread of the virus among already infected cells. The zinc oxide tetrapods (ZnOTs) also exhibit the ability to neutralize HSV-2 virions. Natural target cells such as human vaginal epithelial and HeLa cells showed highly reduced infectivity when infected with HSV-2 virions that were pre-incubated with the ZnOTs. The mechanism behind the ability of ZnOTs to prevent, neutralize or reduce HSV-2 infection relies on their ability to bind the HSV-2 virions. We used fluorescently labeled ZnOTs and GFP-expressing HSV-2 virions to demonstrate the binding of the ZnOTs with HSV-2. We also show that the binding and hence, the antiviral effects of ZnOTs can be enhanced by illuminating the ZnOTs with UV light. Our results provide new insights into the anti-HSV-2 effects of ZnOT and rationalize their development as a HSV-2 trapping agent for the prevention and/or treatment of infection. The observed results also demonstrate that blocking HSV-2 attachment can have prophylactic as well as therapeutic applications.
单纯疱疹病毒 2 型（HSV-2）与靶细胞的附着需要细胞表面带负电荷的辅助受体硫酸乙酰肝素（HS）与病毒包膜糖蛋白 gB 和 gC 上的正电荷残基之间的离子相互作用。有效阻断 HSV-2 发病机制的这第一步显示出对病毒病的显著预防作用；然而，阻断这种相互作用的任何体外治疗效果尚不清楚。在这里，我们提供了新的证据，表明火焰传输方法合成的氧化锌四足微纳米结构显著阻止 HSV-2 进入靶细胞，此外还显示出阻止已感染细胞中病毒传播的潜力。氧化锌四足（ZnOTs）还表现出中和 HSV-2 病毒粒子的能力。当用与 ZnOTs 预孵育的 HSV-2 病毒粒子感染天然靶细胞（如人阴道上皮细胞和 HeLa 细胞）时，这些天然靶细胞的感染性大大降低。ZnOTs 防止、中和或减少 HSV-2 感染的能力背后的机制依赖于它们与 HSV-2 病毒粒子结合的能力。我们使用荧光标记的 ZnOTs 和 GFP 表达的 HSV-2 病毒粒子来证明 ZnOTs 与 HSV-2 的结合。我们还表明，ZnOTs 的结合以及因此其抗病毒作用可以通过用 UV 光照射 ZnOTs 来增强。我们的结果为 ZnOT 对 HSV-2 的抗作用提供了新的见解，并为将其作为 HSV-2 捕获剂用于预防和/或治疗感染提供了合理的依据。观察到的结果还表明，阻断 HSV-2 的附着可以具有预防和治疗应用。
