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Prevention of Avian Retrovirus Infection in Chickens Using CRISPR-Cas9 Delivered by Marek's Disease Virus.
Mol Ther Nucleic Acids. 2020 Jun 12; 21:343-353.MT

Abstract

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.

Authors+Show Affiliations

Avian Immunosuppressive Diseases Division, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.Avian Immunosuppressive Diseases Division, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.Avian Immunosuppressive Diseases Division, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.Avian Immunosuppressive Diseases Division, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.The Pirbright Institute and UK-China Centre of Excellence for Research on Avian Diseases, Pirbright, Ash Road, Guildford, Surrey GU24 0NF, UK.The Pirbright Institute and UK-China Centre of Excellence for Research on Avian Diseases, Pirbright, Ash Road, Guildford, Surrey GU24 0NF, UK.Avian Immunosuppressive Diseases Division, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.Avian Immunosuppressive Diseases Division, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.Avian Immunosuppressive Diseases Division, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.Avian Immunosuppressive Diseases Division, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.Avian Immunosuppressive Diseases Division, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.Avian Immunosuppressive Diseases Division, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China. Electronic address: gaoli@caas.cn.Avian Immunosuppressive Diseases Division, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China. Electronic address: wangxiaomei@caas.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32650233

Citation

Li, Kai, et al. "Prevention of Avian Retrovirus Infection in Chickens Using CRISPR-Cas9 Delivered By Marek's Disease Virus." Molecular Therapy. Nucleic Acids, vol. 21, 2020, pp. 343-353.
Li K, Liu Y, Xu Z, et al. Prevention of Avian Retrovirus Infection in Chickens Using CRISPR-Cas9 Delivered by Marek's Disease Virus. Mol Ther Nucleic Acids. 2020;21:343-353.
Li, K., Liu, Y., Xu, Z., Zhang, Y., Yao, Y., Nair, V., Liu, C., Zhang, Y., Gao, Y., Qi, X., Cui, H., Gao, L., & Wang, X. (2020). Prevention of Avian Retrovirus Infection in Chickens Using CRISPR-Cas9 Delivered by Marek's Disease Virus. Molecular Therapy. Nucleic Acids, 21, 343-353. https://doi.org/10.1016/j.omtn.2020.06.009
Li K, et al. Prevention of Avian Retrovirus Infection in Chickens Using CRISPR-Cas9 Delivered By Marek's Disease Virus. Mol Ther Nucleic Acids. 2020 Jun 12;21:343-353. PubMed PMID: 32650233.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prevention of Avian Retrovirus Infection in Chickens Using CRISPR-Cas9 Delivered by Marek's Disease Virus. AU - Li,Kai, AU - Liu,Yongzhen, AU - Xu,Zengkun, AU - Zhang,Yu, AU - Yao,Yongxiu, AU - Nair,Venugopal, AU - Liu,Changjun, AU - Zhang,Yanping, AU - Gao,Yulong, AU - Qi,Xiaole, AU - Cui,Hongyu, AU - Gao,Li, AU - Wang,Xiaomei, Y1 - 2020/06/12/ PY - 2020/03/22/received PY - 2020/04/13/revised PY - 2020/06/09/accepted PY - 2020/7/11/pubmed PY - 2020/7/11/medline PY - 2020/7/11/entrez KW - CRISPR-Cas9 KW - Marek’s disease virus KW - avian retrovirus KW - vaccine delivery KW - viral infection SP - 343 EP - 353 JF - Molecular therapy. Nucleic acids JO - Mol Ther Nucleic Acids VL - 21 N2 - 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. SN - 2162-2531 UR - https://www.unboundmedicine.com/medline/citation/32650233/Prevention_of_Avian_Retrovirus_Infection_in_Chickens_Using_CRISPR-Cas9_Delivered_by_Marek's_Disease_Virus L2 - https://linkinghub.elsevier.com/retrieve/pii/S2162-2531(20)30170-0 DB - PRIME DP - Unbound Medicine ER -
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