Severe fever with thrombocytopenia syndrome virus (SFTSV) is a bunyavirus that causes SFTS, with a case fatality rate of up to 30 %. The innate immune system plays a crucial role in the defense against SFTSV; however, the impact of viral propagation of STFSV on the innate immune system remains unclear. Although proteomics analysis revealed that the expression of the downregulator of transcription 1 (DR1) increased after SFTSV infection, the specific change trend and the functional role of DR1 during viral infection remain unelucidated. In this study, we demonstrate that DR1 was highly expressed in response to SFTSV infection in HEK 293T cells using qRT-PCR and Western blot analysis. Furthermore, viral replication significantly increased the expression of various TLRs, especially TLR9. Our data indicated that DR1 positively regulated the expression of TLRs in HEK 293T cells, DR1 overexpression highly increased the expression of numerous TLRs, whereas RNAi-mediated DR1 silencing decreased TLR expression. Additionally, the myeloid differentiation primary response gene 88 (MyD88)-dependent or TIR-domain-containing adaptor inducing interferon-β (TRIF)-dependent signaling pathways were highly up- and downregulated by the overexpression and silencing of DR1, respectively. Finally, we report that DR1 stimulates the expression of TLR7, TLR8, and TLR9, thereby upregulating the TRIF-dependent and MyD88-dependent signaling pathways during the SFTSV infection, attenuating viral replication, and enhancing the production of type I interferon and various inflammatory factors, including IL-1β, IL-6, and IL-8. These results imply that DR1 defends against SFTSV replication by inducing the expression of TLR7, TLR8, and TLR9. Collectively, our findings revealed a novel role and mechanism of DR1 in mediating antiviral responses and innate immunity.

严重发热伴血小板减少综合征病毒（SFTSV）是一种引起 SFTS 的布尼亚病毒，病死率高达 30%。先天免疫系统在防御 SFTSV 中发挥着至关重要的作用；然而，STFSV 病毒传播对先天免疫系统的影响仍不清楚。尽管蛋白质组学分析显示SFTSV感染后转录下调因子1（DR1）的表达增加，但DR1在病毒感染过程中的具体变化趋势和功能作用仍不清楚。在本研究中，我们使用 qRT-PCR 和蛋白质印迹分析证明，HEK 293T 细胞中 DR1 在响应 SFTSV 感染时高表达。此外，病毒复制显着增加了各种 TLR 的表达，尤其是 TLR9。我们的数据表明，DR1 正向调节 HEK 293T 细胞中 TLR 的表达，DR1 过表达显着增加了许多 TLR 的表达，而 RNAi 介导的 DR1 沉默降低了 TLR 表达。此外，骨髓分化初级反应基因 88 (MyD88) 依赖性或包含 TIR 结构域的接头诱导干扰素 β (TRIF) 依赖性信号通路分别因 DR1 的过表达和沉默而高度上调和下调。最后，我们报道DR1刺激TLR7、TLR8和TLR9的表达，从而上调SFTSV感染期间TRIF依赖性和MyD88依赖性信号通路，减弱病毒复制，并增强I型干扰素和各种炎症因子的产生，包括 IL-1β、IL-6 和 IL-8。这些结果表明 DR1 通过诱导 TLR7、TLR8 和 TLR9 的表达来防御 SFTSV 复制。总的来说，我们的研究结果揭示了 DR1 在介导抗病毒反应和先天免疫中的新作用和机制。