Negligible contribution of M2634V substitution to ZIKV pathogenesis in AG6 mice revealed by a bacterial promoter activity reduced infectious clone.
Negligible contribution of M2634V substitution to ZIKV pathogenesis in AG6 mice revealed by a bacterial promoter activity reduced infectious clone.
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DOI：
10.1038/s41598-018-28890-0
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发表时间：
2018-07-12
影响因子：
4.6
通讯作者：
Long G
中科院分区：
文献类型：
--
作者：
Zhao F;Xu Y;Lavillette D;Zhong J;Zou G;Long G
ZIKV已经成为严重神经系统并发症的重要人类致病基因，包括成人的格林-巴利综合征（GBS）和各种胎儿畸形，如小头畸形。为了研究ZIKV巴西分离株的致病机制和病毒进化对ZIKV的影响，我们成功构建了ZIKV巴西分离株的感染性cDNA克隆（pZL 1）。pZL 1衍生的病毒能感染不同的细胞系，并对AG 6小鼠产生致死作用。我们进一步研究了NS 5中最近出现的取代（M2634 V）的作用。我们发现回复突变（V2634 M）在多个细胞培养系统中对ZIKV病毒基因组复制和感染性子代产生的影响可忽略不计。此外，该突变不改变ZIKV在AG 6小鼠中的发病机制特征和毒力。总之，我们的结果呈现了来自巴西分离株的另一个稳健的感染性ZIKV克隆，并提供证据支持M2634 V单突变不改变细胞培养物中的病毒生命周期和AG 6小鼠模型中的发病机制。
ZIKV has emerged as a significant human pathogene for the severe neurological complications, including Guillain-Barré(GBS) syndrome in adults and a variety of fetal abnormalities such as microcephaly. A stable and efficient infectious clone of Brazilian ZIKV isolate is required to study pathogenesis of epidemic ZIKV and virus evolution impact on it. Here we successfully constructed infectious cDNA clone on an early Brazilian isolate by eliminating the activity of predicted bacterial promoter in 1–3000 nt of ZIKV genome, leading to a stable infectious cDNA clone (pZL1). pZL1 derived virus could infect different cell lines and cause lethal effect to AG6 mice. We further investigated the role of a recent emerged substitution in NS5 (M2634V). We found that a reverse mutation (V2634M) caused negligible effect on the ZIKV viral genome replication and infectious progeny production in multiple cell culture systems. Additionally, this mutation did not alter the pathogenesis feature and virulence of ZIKV in AG6 mice. In summary, our results present another robust infectious ZIKV clone from Brazilian isolate and provide evidences to support that M2634V single mutation did not alter virus life cycle in cell culture and pathogenesis in AG6 mouse model.
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DOI：
10.1016/0035-9203(81)90100-0
发表时间：
1981-01-01
影响因子：
2.2
作者：
OLSON, JG;KSIAZEK, TG;TRIWIBOWO
通讯作者：
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影响因子：
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通讯作者：
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影响因子：
158.5
作者：
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DOI：
10.1128/genomea.00032-16
发表时间：
2016-03-03
期刊：
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影响因子：
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作者：
Cunha MS;Esposito DL;Rocco IM;Maeda AY;Vasami FG;Nogueira JS;de Souza RP;Suzuki A;Addas-Carvalho M;Barjas-Castro Mde L;Resende MR;Stucchi RS;Boin Ide F;Katz G;Angerami RN;da Fonseca BA
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da Fonseca BA
DOI：
10.1016/0035-9203(54)90006-1
发表时间：
1954-01-01
影响因子：
2.2
作者：
MACNAMARA, FN
通讯作者：
MACNAMARA, FN