Silencing herpes simplex virus type 1 capsid protein encoding genes by siRNA: a promising antiviral therapeutic approach.
Silencing herpes simplex virus type 1 capsid protein encoding genes by siRNA: a promising antiviral therapeutic approach.
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通过 siRNA 沉默单纯疱疹病毒 1 型衣壳蛋白编码基因：一种有前景的抗病毒治疗方法
DOI：
10.1371/journal.pone.0096623
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Jin F;Li S;Zheng K;Zhuo C;Ma K;Chen M;Wang Q;Zhang P;Fan J;Ren Z;Wang Y
单纯疱疹病毒1型(HSV-1)是疱疹病毒科的成员之一，在全球范围内引起多种人类病毒性疾病。尽管有一系列抗病毒药物可用于治疗感染和抑制传播，但HSV-1在世界范围内仍然高度流行。因此，开发具有不同作用机制的新型抗病毒药物迫在眉睫。在HSV-1的增殖过程中，衣壳的组装是病毒生长所必需的，并且在所有的HSV-1株中都是高度保守的。本研究通过筛选针对HSV-1衣壳蛋白的小干扰RNA(SiRNA)，探讨沉默衣壳蛋白表达对HSV-1复制的影响。我们设计并化学合成了针对衣壳基因的siRNAs，通过实时定量聚合酶链式反应检测了其对靶基因表达和细胞内总病毒载量的抑制作用，并通过空斑减少试验和电子显微镜观察了其对HSV-1复制的抑制作用。结果表明，siRNA是体外抑制UL18、UL19、UL26、UL26.5、UL35和UL38衣壳蛋白编码基因表达的有效途径。衣壳蛋白VP23(UL18)和VP5(UL19)单独或联合干扰极大地影响了临床分离的阿昔洛韦耐药HSV-1以及HSV-1/F和HSV-2/333的复制。通过同时敲除UL18和UL19，空斑数量和细胞内病毒粒子显著减少。与病毒对照组相比，UL18和UL19基因敲除组的细胞内总病毒基因组载量也显著降低。结论：干扰UL18和UL19基因的表达可有效抑制HSV-1的体外复制。我们的研究为基于RNA干扰的HSV-1治疗策略提供了新的靶点。
Herpes simplex virus type 1 (HSV-1), a member of the herpesviridae, causes a variety of human viral diseases globally. Although a series of antiviral drugs are available for the treatment of infection and suppression of dissemination, HSV-1 remains highly prevalent worldwide. Therefore, the development of novel antiviral agents with different mechanisms of action is a matter of extreme urgency. During the proliferation of HSV-1, capsid assembly is essential for viral growth, and it is highly conserved in all HSV-1 strains. In this study, small interfering RNAs (siRNAs) against the HSV-1 capsid protein were screened to explore the influence of silencing capsid expression on the replication of HSV-1. We designed and chemically synthesized siRNAs for the capsid gene and assessed their inhibitory effects on the expression of target mRNA and the total intracellular viral genome loads by quantitative real-time PCR, as well as on the replication of HSV-1 via plaque reduction assays and electron microscopy. Our results showed that siRNA was an effective approach to inhibit the expression of capsid protein encoding genes including UL18, UL19, UL26, UL26.5, UL35 and UL38 in vitro. Interference of capsid proteins VP23 (UL18) and VP5 (UL19) individually or jointly greatly affected the replication of clinically isolated acyclovir-resistant HSV-1 as well as HSV-1/F and HSV-2/333. Plaque numbers and intracellular virions were significantly reduced by simultaneous knockdown of UL18 and UL19. The total intracellular viral genome loads were also significantly decreased in the UL18 and UL19 knockdown groups compared with the viral control. In conclusion, interfering with UL18 and UL19 gene expression could inhibit HSV-1 replication efficiently in vitro. Our research offers new targets for an RNA interference-based therapeutic strategy against HSV-1.
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影响因子：
5.4
作者：
Henaff, Daniel;Remillard-Labrosse, Gaudeline;Lippe, Roger
通讯作者：
Lippe, Roger
影响因子：
5.4
作者：
DESAI, P;DELUCA, NA;PERSON, S
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PERSON, S
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影响因子：
4
作者：
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通讯作者：
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影响因子：
64.5
作者：
BOOY, FP;NEWCOMB, WW;STEVEN, AC
通讯作者：
STEVEN, AC
影响因子：
3.7
作者：
Vicentini FT;Borgheti-Cardoso LN;Depieri LV;de Macedo Mano D;Abelha TF;Petrilli R;Bentley MV
通讯作者：
Bentley MV