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序列优化且靶向的双链RNA作为凡纳滨对虾感染性肌坏死病毒的治疗性抗病毒疗法。

Sequence-optimized and targeted double-stranded RNA as a therapeutic antiviral treatment against infectious myonecrosis virus in Litopenaeus vannamei.

作者信息

Loy J Dustin, Loy Duan S, Mogler Mark A, Janke Bruce, Kamrud Kurt, Harris D L Hank, Bartholomay Lyric C

机构信息

Department of Animal Sciences, Iowa State University, Ames, Iowa 50011, USA.

出版信息

Dis Aquat Organ. 2013 Jul 9;105(1):57-64. doi: 10.3354/dao02600.

DOI:10.3354/dao02600
PMID:23836770
Abstract

Infectious myonecrosis virus (IMNV) is a significant and emerging pathogen that has a tremendous impact on the culture of the Pacific white shrimp Litopenaeus vannamei. IMNV first emerged in Brazil in 2002 and subsequently spread to Indonesia, causing large economic losses in both countries. No existing therapeutic treatments or effective interventions currently exist for IMNV. RNA interference (RNAi) is an effective technique for preventing viral disease in shrimp. Here, we describe the efficacy of a double-stranded RNA (dsRNA) applied as an antiviral therapeutic following virus challenge. The antiviral molecule is an optimized dsRNA construct that targets an IMNV sequence at the 5' end of the genome and that showed outstanding antiviral protection previously when administered prior to infection. At least 50% survival is observed with a low dose of dsRNA administered 48 h post-infection with a lethal dose of IMNV; this degree of protection was not observed when dsRNA was administered 72 h post-infection. Additionally, administration of the dsRNA antiviral resulted in a significant reduction of the viral load in the muscle of shrimp that died from disease or survived until termination of the present study, as assessed by quantitative RT-PCR. These data indicate that this optimized RNAi antiviral molecule holds promise for use as an antiviral therapeutic against IMNV.

摘要

传染性肌肉坏死病毒(IMNV)是一种重要的新兴病原体,对凡纳滨对虾的养殖产生了巨大影响。IMNV于2002年首次在巴西出现,随后传播到印度尼西亚,在这两个国家都造成了巨大的经济损失。目前尚无针对IMNV的现有治疗方法或有效干预措施。RNA干扰(RNAi)是预防对虾病毒性疾病的有效技术。在此,我们描述了在病毒攻击后应用双链RNA(dsRNA)作为抗病毒治疗方法的效果。这种抗病毒分子是一种优化的dsRNA构建体,靶向基因组5'端的IMNV序列,并且在感染前给药时先前显示出出色的抗病毒保护作用。在感染致死剂量的IMNV后48小时给予低剂量的dsRNA,观察到至少50%的存活率;在感染后72小时给予dsRNA时未观察到这种程度的保护作用。此外,通过定量RT-PCR评估,给予dsRNA抗病毒药物后,死于疾病或存活至本研究结束的对虾肌肉中的病毒载量显著降低。这些数据表明,这种优化的RNAi抗病毒分子有望用作针对IMNV的抗病毒治疗药物。

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