Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada.
Department of Biochemistry, Microbiology, and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Roger-Guindon Hall Room 4214, Ottawa, ON K1H 8M5 , Canada.
Cells. 2021 Sep 13;10(9):2399. doi: 10.3390/cells10092399.
Survival following Ebola virus (EBOV) infection correlates with the ability to mount an early and robust interferon (IFN) response. The host IFN-induced proteins that contribute to controlling EBOV replication are not fully known. Among the top genes with the strongest early increases in expression after infection in vivo is IFN-induced HERC5. Using a transcription- and replication-competent VLP system, we showed that HERC5 inhibits EBOV virus-like particle (VLP) replication by depleting EBOV mRNAs. The HERC5 RCC1-like domain was necessary and sufficient for this inhibition and did not require zinc finger antiviral protein (ZAP). Moreover, we showed that EBOV (Zaire) glycoprotein (GP) but not Marburg virus GP antagonized HERC5 early during infection. Our data identify a novel 'protagonist-antagonistic' relationship between HERC5 and GP in the early stages of EBOV infection that could be exploited for the development of novel antiviral therapeutics.
埃博拉病毒（EBOV）感染后的存活率与机体早期产生强大干扰素（IFN）反应的能力相关。有助于控制 EBOV 复制的宿主 IFN 诱导蛋白尚未完全明确。在体内感染后表达早期增加最强的基因中，IFN 诱导的 HERC5 排名靠前。我们使用具有转录和复制能力的 VLP 系统表明，HERC5 通过耗尽 EBOV mRNA 来抑制 EBOV 病毒样颗粒（VLP）复制。HERC5 的 RCC1 样结构域是这种抑制所必需的，并且不需要锌指抗病毒蛋白（ZAP）。此外，我们还表明，埃博拉病毒（扎伊尔型）糖蛋白（GP）而非马尔堡病毒 GP 在感染早期拮抗 HERC5。我们的数据确定了在 EBOV 感染的早期阶段，HERC5 和 GP 之间存在一种新的“主角拮抗”关系，这可能被用于开发新型抗病毒治疗药物。
