Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA.
J Virol. 2013 May;87(9):4846-60. doi: 10.1128/JVI.01997-12. Epub 2013 Feb 13.
Rift Valley fever virus (RVFV) is an emerging RNA virus with devastating economic and social consequences. Clinically, RVFV induces a gamut of symptoms ranging from febrile illness to retinitis, hepatic necrosis, hemorrhagic fever, and death. It is known that type I interferon (IFN) responses can be protective against severe pathology; however, it is unknown which innate immune receptor pathways are crucial for mounting this response. Using both in vitro assays and in vivo mucosal mouse challenge, we demonstrate here that RNA helicases are critical for IFN production by immune cells and that signaling through the helicase adaptor molecule MAVS (mitochondrial antiviral signaling) is protective against mortality and more subtle pathology during RVFV infection. In addition, we demonstrate that Toll-like-receptor-mediated signaling is not involved in IFN production, further emphasizing the importance of the RNA cellular helicases in type I IFN responses to RVFV.
裂谷热病毒（RVFV）是一种新兴的 RNA 病毒，具有破坏性的经济和社会后果。临床上，RVFV 引起了一系列症状，从发热病到视网膜炎、肝坏死、出血热和死亡。已知 I 型干扰素（IFN）反应可以预防严重的病理；然而，尚不清楚哪种先天免疫受体途径对这种反应至关重要。我们在这里通过体外测定和体内黏膜小鼠挑战实验表明，RNA 解旋酶对于免疫细胞产生 IFN 至关重要，而通过螺旋酶衔接分子 MAVS（线粒体抗病毒信号）的信号传导对于 RVFV 感染期间的死亡率和更微妙的病理具有保护作用。此外，我们还证明 Toll 样受体介导的信号传导不参与 IFN 的产生，进一步强调了 RNA 细胞解旋酶在 RVFV 对 I 型 IFN 反应中的重要性。
