非洲猪瘟病毒 S273R 蛋白通过干扰 TBK1 和 IRF3 相互作用拮抗 I 型干扰素的产生。
African swine fever virus S273R protein antagonizes type I interferon production by interfering with TBK1 and IRF3 interaction.
机构信息
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China; Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China; Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China; Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China; Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China; Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China; Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
出版信息
Virol Sin. 2023 Dec;38(6):911-921. doi: 10.1016/j.virs.2023.08.009. Epub 2023 Sep 1.
African swine fever (ASF) is originally reported in East Africa as an acute hemorrhagic fever. African swine fever virus (ASFV) is a giant and complex DNA virus with icosahedral structure and encodes a variety of virulence factors to resist host innate immune response. S273R protein (pS273R), as a SUMO-1 specific cysteine protease, can affect viral packaging by cutting polymeric proteins. In this study, we found that pS273R was an important antagonistic viral factor that suppressed cGAS-STING-mediated type I interferon (IFN-I) production. A detailed analysis showed that pS273R inhibited IFN-I production by interacting with interferon regulatory factor 3 (IRF3). Subsequently, we showed that pS273R disrupted the association between TBK1 and IRF3, leading to the repressed IRF3 phosphorylation and dimerization. Deletion and point mutation analysis verified that pS273R impaired IFN-I production independent of its cysteine protease activity. These findings will help us further understand ASFV pathogenesis.
非洲猪瘟（ASF）最初在东非被报道为一种急性出血性发热病。非洲猪瘟病毒（ASFV）是一种具有二十面体结构的巨型和复杂的 DNA 病毒，编码多种毒力因子以抵抗宿主固有免疫反应。S273R 蛋白（pS273R）作为 SUMO-1 特异性半胱氨酸蛋白酶，可以通过切割聚合蛋白来影响病毒包装。在本研究中，我们发现 pS273R 是一种重要的拮抗病毒因子，可抑制 cGAS-STING 介导的 I 型干扰素（IFN-I）产生。详细分析表明，pS273R 通过与干扰素调节因子 3（IRF3）相互作用抑制 IFN-I 的产生。随后，我们表明 pS273R 破坏了 TBK1 和 IRF3 之间的关联，导致 IRF3 磷酸化和二聚化受到抑制。缺失和点突变分析验证了 pS273R 损害 IFN-I 产生不依赖其半胱氨酸蛋白酶活性。这些发现将帮助我们进一步了解 ASFV 的发病机制。
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