Downregulation of transcription 1 hinders the replication of Dabie bandavirus by promoting the expression of TLR7, TLR8, and TLR9 signaling pathway

被引:4
作者
An, Hao [1 ]
Yu, Xiaoli [1 ]
Liu, Yumei [1 ]
Fang, Lei [1 ]
Shu, Ming [1 ]
Zhai, Qingfeng [1 ]
Chen, Junhao [1 ]
机构
[1] Weifang Med Univ, Sch Publ Hlth, Weifang 261053, Peoples R China
关键词
Severe fever with thrombocytopenia virus; Toll-like receptor; Innate immunity; Viral replication; THROMBOCYTOPENIA SYNDROME VIRUS; SEVERE FEVER; NONSTRUCTURAL PROTEIN; INNATE IMMUNITY; POLYMERASE-II; NSS PROTEIN; RNA; NC2; RECOGNITION; INTERFERON;
D O I
10.1016/j.ttbdis.2023.102307
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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-beta (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-1 beta, 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.
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页数:10
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