Herpes Simplex Virus 1 UL2 Inhibits the TNF-α-Mediated NF-κB Activity by Interacting With p65/p50
Herpes Simplex Virus 1 UL2 Inhibits the TNF-α-Mediated NF-κB Activity by Interacting With p65/p50
复制标题
单纯疱疹病毒 1 UL2 通过与 p65/p50 相互作用抑制 TNF-α 介导的 NF-κ B 活性
DOI：
10.3389/fimmu.2020.00549
复制
发表时间：
2020-05-13
影响因子：
7.3
通讯作者：
Li, Meili
中科院分区：
文献类型：
--
作者：
Cai, Mingsheng;Liao, Zongmin;Li, Meili
单纯疱疹病毒1型（HSV - 1）是一种大型双链DNA病毒，它编码至少80种病毒蛋白，其中许多参与病毒 - 宿主相互作用，有利于病毒的生存和繁殖。然而，一些HSV - 1编码蛋白的生物学功能尚未完全了解。核因子κB（NF - κB）的激活是主要的抗病毒先天反应，它可由来自不同途径的细胞受体诱导的各种信号触发。在此，我们证明HSV - 1的UL2蛋白能够拮抗肿瘤坏死因子α（TNF - α）介导的NF - κB激活。免疫共沉淀试验表明，UL2可与NF - κB亚基p65和p50相互作用，这也揭示了UL2的9至17位氨基酸区域能够抑制NF - κB激活，并与p65和p50相互作用，且UL2结合到p65的免疫球蛋白样丛蛋白转录因子功能域。然而，UL2不影响p65 / p50二聚体的形成及其核定位。但是，已证明UL2通过减弱TNF - α诱导的p65在Ser536位点的磷酸化，从而降低下游炎症趋化因子白细胞介素8的表达，来抑制NF - κB的活性。综上所述，UL2对NF - κB激活的减弱可能有助于HSV - 1在感染过程中逃避宿主的抗病毒先天免疫。
Herpes simplex virus 1 (HSV-1) is a large double-stranded DNA virus that encodes at least 80 viral proteins, many of which are involved in the virus-host interaction and are beneficial to the viral survival and reproduction. However, the biological functions of some HSV-1-encoded proteins are not fully understood. Nuclear factor kappa B (NF-kappa B) activation is the major antiviral innate response, which can be triggered by various signals induced by cellular receptors from different pathways. Here, we demonstrated that HSV-1 UL2 protein could antagonize the tumor necrosis factor alpha (TNF-alpha)-mediated NF-kappa B activation. Co-immunoprecipitation assays showed that UL2 could interact with the NF-kappa B subunits p65 and p50, which also revealed the region of amino acids 9 to 17 of UL2 could suppress the NF-kappa B activation and interact with p65 and p50, and UL2 bound to the immunoglobulin-like plexin transcription factor functional domain of p65. However, UL2 did not affect the formation of p65/p50 dimerization and their nuclear localizations. Yet, UL2 was demonstrated to inhibit the NF-kappa B activity by attenuating TNF-alpha-induced p65 phosphorylation at Ser536 and therefore decreasing the expression of downstream inflammatory chemokine interleukin 8. Taken together, the attenuation of NF-kappa B activation by UL2 may contribute to the escape of host's antiviral innate immunity for HSV-1 during its infection.