The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity

	The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity
	Jiao, PT; Ma, JN; Zhao, YN; Jia, XX; Zhang, HR; Fan, WH; Jia, XJ; Bai, XY; Zhao, YQ; Lu, YX; Zhang, H; Guo, JY; Pang, G; Zhang, K; Fang, M; Li, MH; Liu, WJ; Smith, GL; Sun, L
	2024
发表期刊	EMERGING MICROBES & INFECTIONS
ISSN	2222-1751
卷号	13 期号:1
摘要	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 alpha-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.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14384
专题	管理、支撑部门_高等级生物安全灵长类动物实验中心
推荐引用方式 GB/T 7714	Jiao, PT,Ma, JN,Zhao, YN,et al. The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity[J]. EMERGING MICROBES & INFECTIONS,2024,13(1).
APA	Jiao, PT.,Ma, JN.,Zhao, YN.,Jia, XX.,Zhang, HR.,...&Sun, L.(2024).The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity.EMERGING MICROBES & INFECTIONS,13(1).
MLA	Jiao, PT,et al."The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity".EMERGING MICROBES & INFECTIONS 13.1(2024).

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