Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, The Second Affiliated Hospital of Guangzhou Medical University, Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China.
Department of Scientific Research and Education, Yuebei People's Hospital, Shaoguan, China.
Front Immunol. 2020 May 13;11:549. doi: 10.3389/fimmu.2020.00549. eCollection 2020.
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 κB (NF-κB) 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 α (TNF-α)-mediated NF-κB activation. Co-immunoprecipitation assays showed that UL2 could interact with the NF-κB subunits p65 and p50, which also revealed the region of amino acids 9 to 17 of UL2 could suppress the NF-κB 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-κB activity by attenuating TNF-α-induced p65 phosphorylation at Ser536 and therefore decreasing the expression of downstream inflammatory chemokine interleukin 8. Taken together, the attenuation of NF-κB activation by UL2 may contribute to the escape of host's antiviral innate immunity for HSV-1 during its infection.
单纯疱疹病毒 1（HSV-1）是一种大型双链 DNA 病毒，可编码至少 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阐明。核因子 κB（NF-κB）激活是主要的抗病毒先天反应，可以通过来自不同途径的细胞受体诱导的各种信号触发。在这里，我们证明 HSV-1 UL2 蛋白可以拮抗肿瘤坏死因子 α（TNF-α）介导的 NF-κB 激活。共免疫沉淀试验表明 UL2 可以与 NF-κB 亚基 p65 和 p50 相互作用，这也揭示了 UL2 的氨基酸 9 至 17 区域可以抑制 NF-κB 激活并与 p65 和 p50 相互作用，并且 UL2 结合到 p65 的免疫球蛋白样 plexin 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。然而，UL2 通过减弱 TNF-α诱导的 p65 在 Ser536 的磷酸化来抑制 NF-κB 活性，从而减少下游炎症趋化因子白细胞介素 8 的表达。总之，UL2 对 NF-κB 激活的衰减可能有助于 HSV-1 在感染期间逃避宿主的抗病毒先天免疫。
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