Ribavirin efficiently suppresses porcine nidovirus replication.
Ribavirin efficiently suppresses porcine nidovirus replication.
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DOI：
10.1016/j.virusres.2012.10.018
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发表时间：
2013-01
期刊：
影响因子：
5
通讯作者：
Lee C
中科院分区：
文献类型：
--
作者：
Kim Y;Lee C
病毒唑能有效抑制猪巢状病毒感染，并呈剂量依赖性。病毒唑影响PRRSV和PEDV复制周期的进入后步骤。β-GTP耗竭可能是利巴韦林抗猪巢状病毒活性所必需的。利巴韦林不会引发巢病毒基因组的灾难性突变。病毒唑治疗可能是一种很好的抗猪巢状病毒的抗病毒治疗方法。猪繁殖与呼吸综合征病毒（Porcine reproductive and respiratory syndrome virus，PRRSV）和猪流行性腹泻病毒（Porcine epidemic diarrhea virus，PEDV）是两种新型的猪巢状病毒，对养猪业造成严重的经济影响。虽然利巴韦林是一种众所周知的体外抗DNA和RNA病毒的抗病毒药物，但其对猪巢状病毒复制的抑制作用和作用机制仍有待阐明。因此，进行本研究以确定利巴韦林是否抑制猪巢状病毒感染。我们的研究结果表明，利巴韦林治疗剂量依赖性地抑制两种巢病毒的复制。病毒唑对猪巢状病毒复制的抗病毒活性主要在感染后早期发挥。病毒唑治疗导致病毒基因组和亚基因组RNA合成、病毒蛋白表达和子代病毒产生以剂量依赖性方式显著减少。对利巴韦林抗PRRSV和PEDV的作用机制的研究表明，在利巴韦林治疗中加入鸟苷显著逆转了抗病毒作用，表明通过抑制IMP脱氢酶消耗细胞内GTP库可能是利巴韦林活性所必需的。进一步的测序分析显示，利巴韦林处理的细胞中的突变频率与未处理的细胞中的突变频率相似，表明利巴韦林不诱导易错复制。综上所述，我们的数据表明，利巴韦林可能不仅是一个很好的治疗剂对猪巢状病毒，但也是一个潜在的候选人进行评估，对其他人类和动物冠状病毒。
► Ribavirin effectively inhibited porcine nidovirus infection in a dose-dependent manner. ► Ribavirin affected post-entry steps of the replication cycle of PRRSV and PEDV. ► GTP depletion may be essential for the ribavirin activity against porcine nidoviruses. ► Ribavirin did not trigger catastrophic mutations in the nidoviral genome. ► Treatment of ribavirin could be a good antiviral therapy against porcine nidoviruses. Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine epidemic diarrhea virus (PEDV) are porcine nidoviruses that represent emerging viral pathogens causing heavy economic impacts on the swine industry. Although ribavirin is a well-known antiviral drug against a broad range of both DNA and RNA viruses in vitro, its inhibitory effect and mechanism of action on porcine nidovirus replication remains to be elucidated. Therefore, the present study was conducted to determine whether ribavirin suppresses porcine nidovirus infection. Our results demonstrated that ribavirin treatment dose-dependently inhibited the replication of both nidoviruses. The antiviral activity of ribavirin on porcine nidovirus replication was found to be primarily exerted at early times post-infection. Treatment with ribavirin resulted in marked reduction of viral genomic and subgenomic RNA synthesis, viral protein expression, and progeny virus production in a dose-dependent manner. Investigations into the mechanism of action of ribavirin against PRRSV and PEDV revealed that the addition of guanosine to the ribavirin treatment significantly reversed the antiviral effects, suggesting that depletion of the intracellular GTP pool by inhibiting IMP dehydrogenase may be essential for ribavirin activity. Further sequencing analysis showed that the mutation frequency in ribavirin-treated cells was similar to that in untreated cells, indicating that ribavirin did not induce error-prone replication. Taken together, our data indicate that ribavirin might not only be a good therapeutic agent against porcine nidovirus, but also a potential candidate to be evaluated against other human and animal coronaviruses.
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影响因子：
2.2
作者：
ALBINA, E;MADEC, F;TORRISON, J
通讯作者：
TORRISON, J
影响因子：
158.5
作者：
MCCORMICK, JB;KING, IJ;BELMONTWILLIAMS, R
通讯作者：
BELMONTWILLIAMS, R
影响因子：
3.1
作者：
Lee, Yoo Jin;Park, Choi-Kyu;Lee, Changhee
通讯作者：
Lee, Changhee
影响因子：
2.4
作者：
Harms, PA;Sorden, SD;Paul, PS
通讯作者：
Paul, PS
DOI：
10.1073/pnas.96.24.13910
发表时间：
1999-11-23
影响因子：
11.1
作者：
Drake, JW;Holland, JJ
通讯作者：
Holland, JJ