Department of Microbiology, University of Ulsan College of Medicine, Seoul, Korea.
Invest Ophthalmol Vis Sci. 2011 Jan 5;52(1):58-63. doi: 10.1167/iovs.09-5051.
Acute hemorrhagic conjunctivitis (AHC), a highly contagious eye disease, is caused primarily by either enterovirus 70 (EV70) or coxsackievirus A24 (CVA24) infection. Yet methods to prevent or cure AHC are not available. Recent evidence has shown that small-interfering RNAs (siRNAs), mediators of posttranscriptional gene knockdown, can act as effective antiviral agents. Thus, the authors attempted to develop a novel siRNA-based anti-AHC agent effective against both EV70 and CVA24.
Concurrent screening of the entire viral genome sequences of EV70 and CVA24 using the CAPSID program identified five different siRNA candidates complementary to genome regions of both viruses. The antiviral potentials of these siRNAs were assessed by treating MRC5 and primary human conjunctival cells with the siRNAs and following this with viral challenge.
Among the five siRNAs, AHCe-3D-3 siRNA showed excellent cytoprotective effects and dramatic decreases in virus replication and virus protein synthesis. This siRNA, targeting the virus polymerase 3D gene, also induced similar antiviral effects in primary human conjunctival cells.
These findings strongly suggest that the AHCe-3D-3 siRNA, homologous to two different AHC-associated enteroviruses, can provide equivalent antiviral activities against both AHC-causing enteroviruses. Such an siRNA may be developed as a clinically valuable AHC control agent.
急性出血性结膜炎（AHC）是一种高度传染性眼病，主要由肠道病毒 70 型（EV70）或柯萨奇病毒 A24 型（CVA24）感染引起。然而，目前尚无预防或治疗 AHC 的方法。最近的证据表明，小干扰 RNA（siRNA）作为一种有效的抗病毒药物，可作为转录后基因沉默的中介。因此，作者试图开发一种新型的针对 EV70 和 CVA24 的基于 siRNA 的抗 AHC 药物。
使用 CAPSID 程序对 EV70 和 CVA24 的整个病毒基因组序列进行同时筛选，鉴定出与两种病毒基因组区域互补的五个不同的 siRNA 候选物。通过用 siRNA 处理 MRC5 和原代人结膜细胞，并在随后进行病毒攻击，评估这些 siRNA 的抗病毒潜力。
在这 5 个 siRNA 中，AHCe-3D-3 siRNA 显示出极好的细胞保护作用，显著降低了病毒复制和病毒蛋白合成。这种针对病毒聚合酶 3D 基因的 siRNA 也在原代人结膜细胞中诱导了类似的抗病毒作用。
这些发现强烈表明，与两种不同的 AHC 相关肠道病毒同源的 AHCe-3D-3 siRNA 可以对两种引起 AHC 的肠道病毒提供等效的抗病毒活性。这种 siRNA 可能被开发为一种有临床价值的 AHC 控制药物。
