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Identification of Cables1 as a critical host factor that promotes ALV-J replication via genome-wide CRISPR/Cas9 gene knockout screening.
Liu, Peng; Jiang, Jinghua; Chen, Yuntong; Gao, Fei; Wang, Suyan; Yu, Mengmeng; Liu, Yongzhen; Guo, Ru; Zhang, Li; Xu, Zhuangzhuang; Wang, Caiying; Qi, Xiaole; Zhang, Yanping; Cui, Hongyu; Duan, Yulu; Wu, Sen; Gao, Yulong.
Afiliación
  • Liu P; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China.
  • Jiang J; State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, PR China.
  • Chen Y; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China.
  • Gao F; State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, PR China.
  • Wang S; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China.
  • Yu M; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China.
  • Liu Y; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China.
  • Guo R; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China.
  • Zhang L; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China.
  • Xu Z; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China.
  • Wang C; State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, PR China.
  • Qi X; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China.
  • Zhang Y; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China.
  • Cui H; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China.
  • Duan Y; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China.
  • Wu S; State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, PR China. Electronic address: swu@cau.edu.cn.
  • Gao Y; Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Inf
J Biol Chem ; : 107804, 2024 Sep 20.
Article en En | MEDLINE | ID: mdl-39307305
ABSTRACT
Avian leukosis virus subgroup J (ALV-J), a member of the genus Alpharetrovirus, possesses a small genome and exploits a vast array of host factors during its replication cycle. To identify host factors required for ALV-J replication and potentially guide the development of key therapeutic targets for ALV-J prevention, we employed a chicken genome-wide CRISPR/Cas9 knockout library to screen host factors involved in ALV-J infection within DF-1 cells. This screening revealed 42 host factors critical for ALV-J infection. Subsequent knockout assays showed that the absence of the genes encoding cycle-regulatory proteins, namely Cables1, CDK1, and DHFR, significantly inhibited ALV-J replication. Notably, Cables1 knockout cell lines displayed the most pronounced inhibitory effect. Conversely, overexpression assays confirmed that Cables1 significantly promotes ALV-J replication. Immunoprecipitation assays further indicated that Cables1 specifically interacts with the viral protein p15 (viral protease) among all ALV-J proteins, enhancing ALV-J p15 polyubiquitination. Additionally, we identified 26 lysine residues of ALV-J p15 as key sites for ubiquitination, and their replacement with arginine attenuated the replication ability of ALV-J in both in vitro and in vivo assays. This study demonstrates that Cables1 is a critical replication-dependent host factor of ALV-J by enhancing p15 ubiquitination and thereby promoting viral replication. Overall, these findings contribute to a deeper understanding of the ALJ-V replication mechanism and offer a potential target for the prevention and control of ALV-J infection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Biol Chem Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Biol Chem Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos