Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK.
Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
J Gen Virol. 2011 Jul;92(Pt 7):1493-1499. doi: 10.1099/vir.0.030601-0. Epub 2011 Apr 6.
The prophylactic use of topical antiviral agents has recently been validated by the reduction in human immunodeficiency virus (HIV) type 1 infection incidence seen using tonofovir-containing microbicides. In order to develop a wide-spectrum microbicide to prevent infection with a wide range of sexually transmitted viruses, we have previously reported the development of HIV-neutralizing aptamers and here report the isolation and characterization of aptamers that neutralize herpes simplex virus type 2 (HSV-2). These aptamers bind the envelope glycoprotein (gD), are potent (IC(50) of 20-50 nM) and are able to block infection pathways dependent on both major entry receptors, Nectin1 and HVEM. Structural analysis and mutagenesis of these aptamers reveal a core specificity element that could provide the basis for pharmaceutical development. As HSV-2 is a major risk factor for the acquisition of HIV-1, a microbicide capable of preventing HSV-2 infection would not only reduce the morbidity associated with HSV-2, but also that derived from HIV-1.
最近，使用含有替诺福韦的杀微生物剂已证实可降低人类免疫缺陷病毒 (HIV) 1 型感染率，从而验证了局部抗病毒药物的预防作用。为了开发一种广谱杀微生物剂以预防多种性传播病毒的感染，我们之前已经报道了 HIV 中和适体的开发，在此我们报告了分离和鉴定中和单纯疱疹病毒 2 型 (HSV-2) 的适体。这些适体结合包膜糖蛋白 (gD)，具有强大的中和活性（IC50为 20-50 nM），并且能够阻断依赖于主要进入受体 Nectin1 和 HVEM 的感染途径。这些适体的结构分析和突变显示出一个核心特异性元件，这可能为药物开发提供基础。由于 HSV-2 是获得 HIV-1 的主要危险因素，因此能够预防 HSV-2 感染的杀微生物剂不仅会降低与 HSV-2 相关的发病率，还会降低与 HIV-1 相关的发病率。
