Prevention of Avian Retrovirus Infection in Chickens Using CRISPR-Cas9 Delivered by Marek's Disease Virus

文献类型： 外文期刊

第一作者： Li, Kai

作者： Li, Kai;Liu, Yongzhen;Xu, Zengkun;Zhang, Yu;Liu, Changjun;Zhang, Yanping;Gao, Yulong;Qi, Xiaole;Cui, Hongyu;Gao, Li;Wang, Xiaomei;Yao, Yongxiu;Nair, Venugopal;Yao, Yongxiu;Nair, Venugopal

作者机构：

期刊名称：MOLECULAR THERAPY-NUCLEIC ACIDS （ 影响因子：8.886； 五年影响因子：8.334 ）

ISSN： 2162-2531

年卷期： 2020 年 21 卷

页码：

收录情况： SCI

摘要： Reticuloendotheliosis virus (REV) is an avian retrovirus that causes an oncogenic, immunosuppressive, and runting-stunting syndrome in avian hosts. The co-infection of REV and Marek's disease virus (MDV), an oncogenic herpesvirus in chickens, further increases disease severity and reduces MDV vaccine efficacy. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has successfully been used against pathogens in mammalian cells. However, the large size of the CRISPR-Cas9 coding sequences makes its in vivo delivery challenging. Here, following the design of a panel of single-guided RNAs targeting REV, we demonstrate that CRISPR/Cas9 can efficiently mediate the editing of the long terminal repeats of REV, resulting in the inhibition of viral protein expression. The CRISPR-Cas9 system disrupts the integrated proviral genome and provides defense against new viral infection and replication in chicken cells. Moreover, by constructing recombinant MDV carrying CRISPR-Cas9 components using an attenuated MDV vaccine strain as the vector, we efficiently delivered the CRISPR-Cas9 system into chickens, and the MDV-delivered CRISPR-Cas9 drastically reduced REV viral load and significantly diminished REV -associated symptoms. To our knowledge, this is the first study establishing avian retrovirus resistance in chickens utilizing herpesvirus-delivered CRISPR-Cas9, which provides a novel and effective strategy against viral infections.

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