Targeting Herpes Simplex Virus-1 gD by a DNA Aptamer Can Be an Effective New Strategy to Curb Viral Infection.
Targeting Herpes Simplex Virus-1 gD by a DNA Aptamer Can Be an Effective New Strategy to Curb Viral Infection.
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DOI：
10.1016/j.omtn.2017.10.009
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发表时间：
2017-12-15
期刊：
影响因子：
--
通讯作者：
Shukla D
中科院分区：
文献类型：
--
作者：
Yadavalli T;Agelidis A;Jaishankar D;Mangano K;Thakkar N;Penmetcha K;Shukla D
单纯疱疹病毒1型（HSV-1）是发达国家视力丧失的重要因素。HSV-1眼部感染的一个挑战性方面是，普通治疗，如阿昔洛韦，不能提供有效的局部治疗。此外，尚不十分清楚HSV-1进入宿主所需的病毒糖蛋白是否可以靶向用于体内抗眼疱疹的有效治疗。在这里，我们证明了HSV-1包膜糖蛋白gD，这是必不可少的病毒进入和传播，可以特异性地通过局部应用的小DNA适体，以有效地控制眼部感染的病毒。我们的45 nt长的DNA适体显示出对HSV-1 gD的高亲和力（结合亲和力常数[Kd] = 50 nM），其强到足以破坏gD与其同源宿主受体的结合。我们的研究表明，在体外和离体研究中，病毒进入和复制受到显著限制。与随机DNA对照相比，小鼠体内实验也导致预防性治疗下眼部感染的丧失和治疗模式下统计学显著较低的感染。因此，我们的研究验证了靶向HSV-1进入糖蛋白（如gD）可以局部减少感染扩散的可能性，并确定了一种新的基于DNA适体的方法来控制HSV-1的眼部感染。
Herpes simplex virus type 1 (HSV-1) is an important factor for vision loss in developed countries. A challenging aspect of the ocular infection by HSV-1 is that common treatments, such as acyclovir, fail to provide effective topical remedies. Furthermore, it is not very clear whether the viral glycoproteins, required for HSV-1 entry into the host, can be targeted for an effective therapy against ocular herpes in vivo. Here, we demonstrate that HSV-1 envelope glycoprotein gD, which is essential for viral entry and spread, can be specifically targeted by topical applications of a small DNA aptamer to effectively control ocular infection by the virus. Our 45-nt-long DNA aptamer showed high affinity for HSV-1 gD (binding affinity constant [Kd] = 50 nM), which is strong enough to disrupt the binding of gD to its cognate host receptors. Our studies showed significant restriction of viral entry and replication in both in vitro and ex vivo studies. In vivo experiments in mice also resulted in loss of ocular infection under prophylactic treatment and statistically significant lower infection under therapeutic modality compared to random DNA controls. Thus, our studies validate the possibility that targeting HSV-1 entry glycoproteins, such as gD, can locally reduce the spread of infection and define a novel DNA aptamer-based approach to control HSV-1 infection of the eye.
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DOI：
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发表时间：
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期刊：
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影响因子：
--
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