Anti-herpes simplex virus activity of polysaccharides from Eucheuma gelatinae
Anti-herpes simplex virus activity of polysaccharides from Eucheuma gelatinae
复制标题
麒麟菜多糖的抗单纯疱疹病毒活性
DOI：
10.1007/s11274-015-1798-1
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发表时间：
2015-03-01
影响因子：
4.1
通讯作者：
Wang, Yifei
中科院分区：
文献类型：
--
作者：
Jin, Fujun;Zhuo, Cuiqin;Wang, Yifei
摘要
阿昔洛韦是治疗单纯疱疹病毒（HSV）感染的常用药物，但随着其广泛的临床应用，越来越多的耐药株被发现，因此寻找一种能对抗阿昔洛韦耐药病毒的药物已成为药物筛选和开发的重要目标。本研究采用空斑减数实验、实时荧光定量PCR、免疫印迹和免疫荧光技术研究琼枝麒麟菜多糖（Eucheuma gelatae polysaccharide，EGP）对HSV的抗病毒作用，并初步阐明EGP体外抗HSV的作用机制。EGP在体外对HSV感染有明显的抑制作用，对阿昔洛韦耐药株有较好的抑制作用。更详细的实验表明，EGP通过直接灭活HSV-1颗粒和破坏病毒附着来预防早期HSV-1感染，但对病毒穿透没有影响。EGP还能抑制HSV-1早期基因和晚期基因的RNA合成以及病毒DNA的复制，但对即刻早期基因的合成无影响。此外，通过免疫荧光和western blot检测，我们发现EGP对HSV-1的蛋白质合成有明显的影响。这些结果表明，EGP主要通过抑制HSV-1早期感染和抑制病毒RNA和DNA合成来发挥其抗HSV-1的活性。EGP具有较弱的细胞毒性、较强的病毒灭活和粘附抑制活性，使其成为HSV治疗的候选杀病毒剂，特别是对于耐药株。
Abstract
Acyclovir is a commonly-used drug for treating herpes simplex virus (HSV) infections, but with its wide clinical application, more and more resistant strains have been found. Therefore, seeking a drug that can act against acyclovir-resistant virus has become an important goal of drug screening and development. In this study, plaque reduction assay, real-time PCR, Western blot, and immunofluorescence technique were used to investigate the antiviral effect of Eucheuma gelatinae polysaccharide (EGP) on HSV and to preliminarily clarify the in vitro anti-HSV mechanism of EGP. EGP was found to significantly inhibit HSV infection in vitro and displayed a good inhibitory effect on acyclovir-resistant strains. More detailed experiments have shown that EGP prevented early HSV-1 infection through directly inactivating HSV-1 particles and impairing virus attachment, but without effect on viral penetration. EGP also inhibited the RNA synthesis of HSV-1 early gene and late gene as well as viral DNA replication; no effect on immediate-early gene synthesis was observed. Besides, through immunofluorescence and western blot, we found that EGP significantly affected the protein synthesis of HSV-1. Taken together, these results demonstrate that EGP exerts its anti-HSV activity mainly through impeding early HSV-1 infection and inhibiting viral RNA and DNA syntheses. The weak cytotoxicity, strong viral inactivation as well as attachment inhibition activity enable EGP to be a virucide candidate for HSV therapy, especially for drug-resistant strains.