Marek's Disease Virus Cluster 3 miRNAs Restrict Virus' Early Cytolytic Replication and Pathogenesis.
Marek's Disease Virus Cluster 3 miRNAs Restrict Virus' Early Cytolytic Replication and Pathogenesis.
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马立克氏病病毒簇3 miRNAs限制病毒的早期溶细胞复制和致病机制
DOI：
10.3390/v12111317
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发表时间：
2020-11-17
期刊：
影响因子：
--
通讯作者：
Reddy SM
中科院分区：
文献类型：
--
作者：
Liao Y;Zhuang G;Sun A;Khan OA;Lupiani B;Reddy SM
在受感染的细胞中发现了疱疹病毒编码的 microRNA (miRNA)；然而，缺乏合适的动物模型阻碍了病毒 miRNA 的体内功能分析。马立克氏病病毒 (MDV)（Gallid alphaherpesvirus 2，GaHV-2）基因组包含 14 个 miRNA 前体，编码 26 个成熟 miRNA，分为三个簇。在这项研究中，MDV 编码的簇 3 miRNA（也称为 mdv1-miR-M8-M10）在 MDV 天然宿主鸡的发病机制中的作用进行了评估。我们的结果表明，删除簇 3 miRNA 不会影响细胞培养物中的病毒复制和噬斑大小，但会增加鸡中 MDV 的早期溶细胞复制。我们还观察到，删除簇 3 miRNA 会导致外周血淋巴细胞的病毒再激活显着增加。此外，发病机制研究表明，删除cluster 3 miRNA会导致更严重的淋巴器官萎缩并缩短平均死亡时间，但并不影响MDV相关内脏肿瘤的发生率。我们通过生成簇 3 miRNA 回复病毒证实了这些结果，其中亲本 MDV 表型得到恢复。据我们所知，我们的研究提供了第一个证据，证明 MDV cluster 3 miRNA 在调节 MDV 发病机制中发挥着重要作用。
Herpesvirus-encoded microRNAs (miRNAs) have been discovered in infected cells; however, lack of a suitable animal model has hampered functional analyses of viral miRNAs in vivo. Marek’s disease virus (MDV) (Gallid alphaherpesvirus 2, GaHV-2) genome contains 14 miRNA precursors, which encode 26 mature miRNAs, grouped into three clusters. In this study, the role of MDV-encoded cluster 3 miRNAs, also known as mdv1-miR-M8-M10, in pathogenesis was evaluated in chickens, the natural host of MDV. Our results show that deletion of cluster 3 miRNAs did not affect virus replication and plaque size in cell culture, but increased early cytolytic replication of MDV in chickens. We also observed that deletion of cluster 3 miRNAs resulted in significantly higher virus reactivation from peripheral blood lymphocytes. In addition, pathogenesis studies showed that deletion of cluster 3 miRNAs resulted in more severe atrophy of lymphoid organs and reduced mean death time, but did not affect the incidence of MDV-associated visceral tumors. We confirmed these results by generating a cluster 3 miRNA revertant virus in which the parental MDV phenotype was restored. To the best of our knowledge, our study provides the first evidence that MDV cluster 3 miRNAs play an important role in modulating MDV pathogenesis.
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影响因子：
5.4
作者：
Cui, XP;Lee, LF;Reddy, SM
通讯作者：
Reddy, SM
影响因子：
6.7
作者：
Kincaid RP;Sullivan CS
通讯作者：
Sullivan CS
DOI：
10.1073/pnas.0404508101
发表时间：
2004-08-10
影响因子：
11.1
作者：
Lupiani, B;Lee, LF;Reddy, SM
通讯作者：
Reddy, SM
影响因子：
5.4
作者：
Burnside, Joan;Bernberg, Erin;Morgan, Robin W.
通讯作者：
Morgan, Robin W.
影响因子：
5.4
作者：
Kamil, JP;Tischer, BK;Kung, HJ
通讯作者：
Kung, HJ