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Pseudorabies virus kinase UL13 phosphorylates H2AX to foster viral replication.
Ming, Xin; Bo, Zongyi; Miao, Yurun; Chen, Huan; Bao, Chenyi; Sun, Liumei; Xi, Rui; Zhong, Qiuping; Zhao, Pu; Jung, Yong-Sam; Qian, Yingjuan.
Afiliação
  • Ming X; MOE Joint International Research Laboratory of Animal Health and Food Safety, MOA Key Laboratory of Animal Bacteriology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Bo Z; MOE Joint International Research Laboratory of Animal Health and Food Safety, MOA Key Laboratory of Animal Bacteriology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Miao Y; Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, China.
  • Chen H; MOE Joint International Research Laboratory of Animal Health and Food Safety, MOA Key Laboratory of Animal Bacteriology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Bao C; MOE Joint International Research Laboratory of Animal Health and Food Safety, MOA Key Laboratory of Animal Bacteriology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Sun L; MOE Joint International Research Laboratory of Animal Health and Food Safety, MOA Key Laboratory of Animal Bacteriology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Xi R; MOE Joint International Research Laboratory of Animal Health and Food Safety, MOA Key Laboratory of Animal Bacteriology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Zhong Q; MOE Joint International Research Laboratory of Animal Health and Food Safety, MOA Key Laboratory of Animal Bacteriology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Zhao P; MOE Joint International Research Laboratory of Animal Health and Food Safety, MOA Key Laboratory of Animal Bacteriology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Jung YS; MOE Joint International Research Laboratory of Animal Health and Food Safety, MOA Key Laboratory of Animal Bacteriology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • Qian Y; MOE Joint International Research Laboratory of Animal Health and Food Safety, MOA Key Laboratory of Animal Bacteriology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
FASEB J ; 36(3): e22221, 2022 03.
Article em En | MEDLINE | ID: mdl-35199383
The DNA damage response (DDR) pathway is critical for maintaining genomic integrity and sustaining organismal development. Viruses can either utilize or circumvent the DDR to facilitate their replication. Pseudorabies virus (PRV) infection was shown to induce apoptosis via stimulating DDR. However, the underlying mechanisms have not been fully explored to date. This study showed that PRV infection robustly activates the ATM and DNA-PK signaling pathways shortly after infection. However, inhibition of ATM, but not DNA-PK, could dampen PRV replication in cells. Importantly, we found that PRV-encoded serine/threonine kinase UL13 interacts with and subsequently phosphorylates H2AX. Furthermore, we found that UL13 deletion largely attenuates PRV neuroinvasiveness and virulence in vivo. In addtion, we showed that UL13 contributes to H2AX phosphorylation upon PRV infection both in vitro and in vivo, but does not affect ATM phosphorylation. Finally, we showed that knockdown of H2AX reduces PRV replication, while this reduction can be further enhanced by deletion of UL13. Taken together, we conclude that PRV-encoded kinase UL13 regulates DNA damage marker γH2AX and UL13-mediated H2AX phosphorylation plays a pivotal role in efficient PRV replication and progeny production.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Quinases / Pseudorraiva / Proteínas Virais / Replicação Viral / Histonas / Herpesvirus Suídeo 1 Limite: Animals / Female / Humans Idioma: En Revista: FASEB J Assunto da revista: BIOLOGIA / FISIOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Quinases / Pseudorraiva / Proteínas Virais / Replicação Viral / Histonas / Herpesvirus Suídeo 1 Limite: Animals / Female / Humans Idioma: En Revista: FASEB J Assunto da revista: BIOLOGIA / FISIOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China