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The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity.
Jiao, Pengtao; Ma, Jianing; Zhao, Yuna; Jia, Xiaoxiao; Zhang, Haoran; Fan, Wenhui; Jia, Xiaojuan; Bai, Xiaoyuan; Zhao, Yiqi; Lu, Yongxu; Zhang, He; Guo, Jiayin; Pang, Gang; Zhang, Ke; Fang, Min; Li, Minghua; Liu, Wenjun; Smith, Geoffrey L; Sun, Lei.
Afiliação
  • Jiao P; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Ma J; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Zhao Y; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Jia X; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Zhang H; College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning, People's Republic of China.
  • Fan W; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Jia X; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Bai X; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Zhao Y; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Lu Y; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Zhang H; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Guo J; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
  • Pang G; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
  • Zhang K; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, People's Republic of China.
  • Fang M; Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, People's Republic of China.
  • Li M; Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, People's Republic of China.
  • Liu W; Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, People's Republic of China.
  • Smith GL; School of Life Sciences, Henan University, Kaifeng, People's Republic of China.
  • Sun L; Kunming National High-level Biosafety Research Center for Non-Human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People's Republic of China.
Emerg Microbes Infect ; 13(1): 2372344, 2024 Dec.
Article em En | MEDLINE | ID: mdl-38916407
ABSTRACT
The Orthopoxvirus (OPXV) genus of the Poxviridae includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the P2L gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Virais / Monkeypox virus / Sinais de Localização Nuclear / Fator Regulador 3 de Interferon / Imunidade Inata Limite: Animals / Humans Idioma: En Revista: Emerg Microbes Infect Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Virais / Monkeypox virus / Sinais de Localização Nuclear / Fator Regulador 3 de Interferon / Imunidade Inata Limite: Animals / Humans Idioma: En Revista: Emerg Microbes Infect Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos