A Simple and Robust Approach for Evaluation of Antivirals Using a Recombinant Influenza Virus Expressing Gaussia Luciferase.
A Simple and Robust Approach for Evaluation of Antivirals Using a Recombinant Influenza Virus Expressing Gaussia Luciferase.
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使用表达高斯荧光素酶的重组流感病毒评估抗病毒药物的简单而稳健的方法
DOI：
10.3390/v10060325
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发表时间：
2018-06-13
期刊：
影响因子：
--
通讯作者：
Du R
中科院分区：
文献类型：
--
作者：
Li P;Cui Q;Wang L;Zhao X;Zhang Y;Manicassamy B;Yang Y;Rong L;Du R
甲型流感病毒（IAV）引起季节性流行病和偶尔但毁灭性的大流行，这是主要的公共卫生问题。由于季节性疫苗的有效性变化很大，目前可用的药物由于耐药性的出现而效力有限，因此迫切需要开发新的抗病毒药物。在这项研究中，我们的特点是重组IAV携带Gaussia荧光素酶（Gluc）基因，并确定其作为评估治疗方法的工具的潜力。我们证明，这种重组IAV在组织培养中具有复制能力，并且在小鼠中具有致病性，尽管与亲本病毒相比，它略微减毒。荧光素酶的表达与病毒在体外和体内的繁殖密切相关，为组织培养和小鼠肺中的病毒复制提供了一种简单的测量方法。为了证明这种病毒的效用，利巴韦林和磷酸奥司他韦被用来治疗IAV感染的细胞和小鼠，我们观察到剂量依赖性抑制病毒复制的荧光素酶测定。此外，感染肺中荧光素酶表达的降低可以预测早在病毒攻击后第2天的抗病毒干预的保护效果。总之，这项研究提供了一个新的和定量的方法来评估抗病毒药物对IAV。
Influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are major public health concerns. Because the effectiveness of seasonal vaccines is highly variable and the currently available drugs are limited in their efficacy because of the emergence of drug resistance, there is an urgent need to develop novel antivirals. In this study, we characterized a recombinant IAV-carrying Gaussia luciferase (Gluc) gene and determined its potential as a tool for evaluating therapeutics. We demonstrated that this recombinant IAV is replication-competent in tissue culture and pathogenic in mice, although it is slightly attenuated compared to the parental virus. Luciferase expression correlated well with virus propagation both in vitro and in vivo, providing a simple measure for viral replication in tissue culture and in mouse lungs. To demonstrate the utility of this virus, ribavirin and oseltamivir phosphate were used to treat the IAV-infected cells and mice, and we observed the dose-dependent inhibition of viral replication by a luciferase assay. Moreover, the decreased luciferase expression in the infected lungs could predict the protective efficacy of antiviral interventions as early as day 2 post virus challenge. In summary, this study provides a new and quantitative approach to evaluate antivirals against IAV.
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影响因子：
6.4
作者：
Czakó R;Vogel L;Lamirande EW;Bock KW;Moore IN;Ellebedy AH;Ahmed R;Mehle A;Subbarao K
通讯作者：
Subbarao K
影响因子：
46.9
作者：
Cabantous, S;Terwilliger, TC;Waldo, GS
通讯作者：
Waldo, GS
影响因子：
5.4
作者：
Chen, Grace L.;Lamirande, Elaine W.;Subbarao, Kanta
通讯作者：
Subbarao, Kanta
影响因子：
5.6
作者：
Nogales A;Martínez-Sobrido L
通讯作者：
Martínez-Sobrido L
DOI：
10.1038/nrd2175
发表时间：
2006-12
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
De Clercq E
通讯作者：
De Clercq E