Department of Microbiology and Infection Control, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki 569-8686, Japan.
Department of Biochemistry, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki 569-8686, Japan.
Int J Mol Sci. 2022 Oct 20;23(20):12619. doi: 10.3390/ijms232012619.
Flaviviruses (the genus of the family) include many arthropod-borne viruses, often causing life-threatening diseases in humans, such as hemorrhaging and encephalitis. Although the flaviviruses have a significant clinical impact, it has become apparent that flavivirus replication is restricted by cellular factors induced by the interferon (IFN) response, which are called IFN-stimulated genes (ISGs). SHFL (shiftless antiviral inhibitor of ribosomal frameshifting) is a novel ISG that inhibits dengue virus (DENV), West Nile virus (WNV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) infections. Interestingly, SHFL functions as a broad-spectrum antiviral factor exhibiting suppressive activity against various types of RNA and DNA viruses. In this review, we summarize the current understanding of the molecular mechanisms by which SHFL inhibits flavivirus infection and discuss the molecular basis of the inhibitory mechanism using a predicted tertiary structure of SHFL generated by the program AlphaFold2.
黄病毒（属 科）包括许多节肢动物传播的病毒，这些病毒常导致人类出现危及生命的疾病，如出血和脑炎。尽管黄病毒具有重大的临床影响，但已明显表明黄病毒的复制受到干扰素（IFN）反应诱导的细胞因子的限制，这些细胞因子被称为干扰素刺激基因（ISG）。SHFL（核糖体移码无移位抗病毒抑制剂）是一种新的 ISG，可抑制登革热病毒（DENV）、西尼罗河病毒（WNV）、寨卡病毒（ZIKV）和日本脑炎病毒（JEV）感染。有趣的是，SHFL 作为一种广谱抗病毒因子，对各种类型的 RNA 和 DNA 病毒均具有抑制活性。在这篇综述中，我们总结了目前对 SHFL 抑制黄病毒感染的分子机制的理解，并使用由 AlphaFold2 程序生成的 SHFL 的预测三级结构讨论了抑制机制的分子基础。
