Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, 55905, USA.
Mayo Clinic, Department of Molecular Medicine, Rochester, MN, 55905, USA.
Antiviral Res. 2021 Jan;185:104993. doi: 10.1016/j.antiviral.2020.104993. Epub 2020 Dec 6.
Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV) cause viral hemorrhagic fever-like illnesses in humans due to an aberrant host inflammatory response, which contributes to pathogenesis. Here, we established two separate minigenome (MG) systems based on the M-segment of SFTSV and HRTV. Following characterization of both systems for SFTSV and HRTV, we used them as a platform to screen potential compounds that inhibit viral RNA synthesis. We demonstrated that the NF-κB inhibitor, SC75741, reduces viral RNA synthesis of SFTSV and HRTV using our MG platform and validated these results using infectious SFTSV and HRTV. These results may lead to the use of MG systems as potential screening systems for the identification of antiviral compounds and yield novel insights into host-factors that could play role in bandavirus transcription and replication.
严重发热伴血小板减少综合征病毒 (SFTSV) 和 Heartland 病毒 (HRTV) 通过宿主异常炎症反应引起类似病毒性出血热的疾病，这有助于发病机制。在这里，我们建立了两个基于 SFTSV 和 HRTV 的 M 片段的独立小基因组 (MG) 系统。在对 SFTSV 和 HRTV 的两个系统进行特征描述后，我们将其用作筛选潜在抑制病毒 RNA 合成的化合物的平台。我们证明 NF-κB 抑制剂 SC75741 使用我们的 MG 平台降低 SFTSV 和 HRTV 的病毒 RNA 合成，并使用传染性 SFTSV 和 HRTV 验证了这些结果。这些结果可能导致 MG 系统被用作鉴定抗病毒化合物的潜在筛选系统，并为可能在班达病毒转录和复制中发挥作用的宿主因子提供新的见解。
