Purpose : To investigate the activity and mechanism of action of arbidol against Hantaan virus (HTNV) activity by modulating inflammation via TLR-4 pathway. Methods : HUVEC cells infected with HTNV 76-118 were treated with serially diluted arbidol solutions at -2h (2 h before viral infection, pre-treatment mode), 0 h (at the same time as viral infection, simultaneous treatment mode) or 2 h (2 h after viral infection, post-treatment mode). The transcript levels of TLR4 were detected by semi-quantitative reverse transcription-PCR (RT-PCR) at 6, 12, 18, and 24 h later. The levels of iNOS and TNF-α were examined using enzyme-linked immunosorbent assay (ELISA). Results : Pre-treatment with arbidol, rather than simultaneous treatment or post-treatment, effectively inhibited up-regulation of cellular TLR4 expression (up to 40 ± 6.1 % inhibition) and activity of supernatant iNOS induced by HTNV infection(up to 44.1 ± 9.4 % inhibition), as well as in a LPSstimulated inflammatory endothelial cell. Arbidol decreased the elevated TNF-α levels induced by LPS stimulation. Conclusion : These results are the first evidence that arbidol modulates viral PRRs signaling and its consequential inflammatory cytokine/chemokine response during hantavirus infection. Keywords : Hantavirus , Arbidol, Toll-like receptors, inducible nitric oxide synthase, Antiviral activity, Inflammation

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阿比多尔抗汉坦病毒感染的抗病毒活性及其作用机理

目的：通过调节TLR-4途径的炎症反应，探讨阿比多尔抗汉坦病毒（HTNV）活性的活性及其作用机理。方法：在感染后2小时（病毒感染前2小时，预处理模式），0小时（病毒感染同时，同时处理模式）或-2小时，用连续稀释的阿比多尔溶液处理感染了HTNV 76-118的HUVEC细胞。 h（病毒感染后2 h，后处理模式）。在6、12、18和24小时后，通过半定量逆转录PCR（RT-PCR）检测TLR4的转录水平。使用酶联免疫吸附测定（ELISA）检测iNOS和TNF-α的水平。结果：用阿比多尔进行预处理，而不是同时进行治疗或后处理，可以有效抑制细胞TLR4表达的上调（最高40±6）。1％的抑制）和HTNV感染诱导的上清液iNOS的活性（高达44.1±9.4％抑制），以及LPS刺激的炎症内皮细胞。Arbidol降低了LPS刺激诱导的TNF-α水平升高。结论：这些结果是arbidol在汉坦病毒感染过程中调节病毒PRRs信号传导及其相应的炎性细胞因子/趋化因子反应的第一个证据。关键词：汉坦病毒，阿比多尔，Toll样受体，诱导型一氧化氮合酶，抗病毒活性，炎症 这些结果是在汉坦病毒感染期间arbidol调节病毒PRRs信号传导及其相应的炎性细胞因子/趋化因子反应的第一个证据。关键词：汉坦病毒，阿比多尔，Toll样受体，诱导型一氧化氮合酶，抗病毒活性，炎症 这些结果是在汉坦病毒感染期间arbidol调节病毒PRRs信号传导及其相应的炎性细胞因子/趋化因子反应的第一个证据。关键词：汉坦病毒，阿比多尔，Toll样受体，诱导型一氧化氮合酶，抗病毒活性，炎症