Antiviral potency of a siRNA targeting a conserved region of coxsackievirus A24
Antiviral potency of a siRNA targeting a conserved region of coxsackievirus A24
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DOI：
10.1016/j.bbrc.2008.08.169
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发表时间：
2008-11-14
影响因子：
3.1
通讯作者：
Lee, Heuiran
中科院分区：
文献类型：
--
作者：
Jun, Eun Jung;Nam, Young Ran;Lee, Heuiran
柯萨奇病毒A24（CVA 24）是导致急性出血性结膜炎的原因，急性出血性结膜炎是一种高度传染性的眼病，目前尚无预防或治疗方法。因此，我们评估了靶向CVA 24的小干扰RNA（siRNA）的抗病毒潜力。用各种CVA 24攻击具有或不具有与2C或3D基因组区域互补的四种不同siRNA的HeLa细胞。在几种siRNA中，靶向被称为顺式作用复制元件（CVA 24-CRE）的高度保守的基因组区域的siRNA是唯一降低CVA 24变体和临床分离株的病毒复制和随后的细胞毒性的siRNA。此外，CVA 24-CRE在原代人结膜细胞中对CVA 24具有有效的抗病毒活性。此外，CVA 24-CRE对遗传改变的逃逸突变体的出现具有高度抗性。总的来说，本研究提供的证据表明，靶向保守的病毒基因组区域的CVA 24-CRE具有普遍的、延长的抗CVA 24活性。因此，这种siRNA可能具有临床上作为新型抗CVA 24剂的潜力。(C)2008年爱思唯尔公司All rights reserved.
Coxsackievirus A24 (CVA24) is responsible for acute hemorrhagic conjunctivitis, a highly contagious eye disease for which no prevention or treatment is Currently available. We thus assessed the antiviral potential of a small interfering RNA (siRNA) targeting CVA24. HeLa cells with or without four different siRNAs complementary to 2C or 3D genome region, were challenged with various CVA24s. Among several siRNAs, a siRNA targeting the highly conserved genome region called the cis-acting replication element (CVA24-CRE), was the only siRNA that decreased virus replication and Subsequent cytotoxicity by both CVA24 variant and clinical isolates. Furthermore, CVA24-CRE had effective antiviral activity against CVA24 in primary human conjunctival cells. In addition, CVA24-CRE was highly resistant to the emergence of genetically altered escape mutants. Collectively, the present Study provides evidence that CVA24-CRE targeting a conserved viral genome region had universal, prolonged anti-CVA24 activity. This siRNA may thus hold a potential to act clinically as a novel anti-CVA24 agent. (C) 2008 Elsevier Inc. All rights reserved.