Adenovirus-mediated artificial MicroRNAs targeting matrix or nucleoprotein genes protect mice against lethal influenza virus challenge
Adenovirus-mediated artificial MicroRNAs targeting matrix or nucleoprotein genes protect mice against lethal influenza virus challenge
复制标题
腺病毒介导的人工MicroRNA靶向基质或核蛋白基因可保护小鼠免受致命流感病毒的攻击
DOI：
10.1038/gt.2015.31
复制
发表时间：
2015-08-01
期刊：
影响因子：
5.1
通讯作者：
Zhou, D.
中科院分区：
文献类型：
--
作者：
Zhang, H.;Tang, X.;Zhou, D.
流感病毒(IV)感染是一个重大的公共卫生问题，每年在全世界造成数百万例严重疾病和多达50万人死亡。鉴于目前预防或治疗急性流感的局限性，需要新的治疗方法。通过microRNAs的RNA干扰(RNAi)(MiRNA)是一种在体外和体内抑制病毒复制的新兴技术。在这里，我们描述了一种新的治疗流感的策略，该策略基于由复制缺陷型腺病毒(AdC68)载体传递的RNAi，该载体来源于黑猩猩血清68型(AdC68)。我们的结果表明，针对IV基因组保守区的人工miRNAs(AmiRNAs)可以有效地抑制病毒在人胚胎肾脏293细胞中的复制。此外，我们的结果表明，针对IV病毒M1、M2或核蛋白基因表达amRNA的AdC68预防性治疗完全保护小鼠免受同源A/PR8病毒攻击，并部分保护小鼠免受异种甲型流感病毒株如H9N2和H5N1的攻击。总之，我们的数据表明，针对A型流感病毒保守区的amiRNAs可以作为预防人类和动物IV感染的一种新策略。
Influenza virus (IV) infection is a major public health problem, causing millions of cases of severe illness and as many as 500 000 deaths each year worldwide. Given the limitations of current prevention or treatment of acute influenza, novel therapies are needed. RNA interference (RNAi) through microRNAs (miRNA) is an emerging technology that can suppress virus replication in vitro and in vivo. Here, we describe a novel strategy for the treatment of infuenza based on RNAi delivered by a replication-defective adenovirus (Ad) vector, derived from chimpanzee serotype 68 (AdC68). Our results showed that artificial miRNAs (amiRNAs) specifically targeting conserved regions of the IV genome could effectively inhibit virus replication in human embryonic kidney 293 cells. Moreover, our results demonstrated that prophylactic treatment with AdC68 expressing amiRNAs directed against M1, M2 or nucleoprotein genes of IV completely protected mice from homologous A/PR8 virus challenge and partially protected the mice from heterologous influenza A virus strains such as H9N2 and H5N1. Collectively, our data demonstrate that amiRNAs targeting the conserved regions of influenza A virus delivered by Ad vectors should be pursued as a novel strategy for prophylaxis of IV infection in humans and animals.