Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, 26 Huacai Road, Chengdu, 610051, China.
The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Virol J. 2021 Dec 20;18(1):256. doi: 10.1186/s12985-021-01724-8.
Although interferon regulatory factor 2 (IRF2) was reported to stimulate virus replication by suppressing the type I interferon signaling pathway, because cell cycle arrest was found to promote viral replication, IRF2-regulated replication fork factor (FAM111A and RFC3) might be able to affect ZIKV replication. In this study, we aimed to investigate the function of IRF2, FAM111A and RFC3 to ZIKV replication and underlying mechanism.
siIRF2, siFAM111A, siRFC3 and pIRF2 in ZIKV-infected A549, 2FTGH and U5A cells were used to explore the mechanism of IRF2 to inhibit ZIKV replication. In addition, their expression was analyzed by RT-qPCR and western blots, respectively.
In this study, we found IRF2 expression was increased in ZIKV-infected A549 cells and IRF2 inhibited ZIKV replication independent of type I IFN signaling pathway. IRF2 could activate FAM111A expression and then enhanced the host restriction effect of RFC3 to inhibit replication of ZIKV.
We speculated the type I interferon signaling pathway might not play a leading role in regulating ZIKV replication in IRF2-silenced cells. We found IRF2 was able to upregulate FAM111A expression and thus enhance the host restriction effect of RFC3 on ZIKV.
干扰素调节因子 2（IRF2）通过抑制 I 型干扰素信号通路被报道能刺激病毒复制，但由于细胞周期停滞被发现能促进病毒复制，IRF2 调节的复制叉因子（FAM111A 和 RFC3）可能能够影响 ZIKV 的复制。在本研究中，我们旨在研究 IRF2、FAM111A 和 RFC3 对 ZIKV 复制的功能及其潜在机制。
用 siIRF2、siFAM111A、siRFC3 和 pIRF2 处理感染 ZIKV 的 A549、2FTGH 和 U5A 细胞，以探讨 IRF2 抑制 ZIKV 复制的机制。此外，分别通过 RT-qPCR 和 Western blot 分析它们的表达。
在本研究中，我们发现 ZIKV 感染的 A549 细胞中 IRF2 的表达增加，IRF2 抑制 ZIKV 复制不依赖于 I 型 IFN 信号通路。IRF2 可以激活 FAM111A 的表达，从而增强 RFC3 对 ZIKV 复制的宿主限制作用。
我们推测在 IRF2 沉默的细胞中，I 型干扰素信号通路可能在调节 ZIKV 复制中不起主导作用。我们发现 IRF2 能够上调 FAM111A 的表达，从而增强 RFC3 对 ZIKV 的宿主限制作用。
