The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function

Yang, Darong; Li, Nan L.; Wei, Dahai; Liu, Baoming; Guo, Fang; Elbahesh, Husni; Zhang, Yunzhi; Zhou, Zhi; Chen, Guo-Yun; Li, Kui

Host cells are equipped with exquisite, intrinsic mechanisms to fend off invading viruses, which could be harnessed for developing antivirals against flaviviruses, including ZIKV. The mammalian innate immune system constitutes the first line of defense against invading microorganisms including viral pathogens. A hallmark of the intrinsic antiviral responses is the rapid induction of interferons (IFNs). Once produced, IFNs act in a paracrine and/or autocrine fashion, signaling through cell surface IFN receptors and downstream Jak-Stat pathway, culminating in the upregulation of hundreds of IFN-stimulated gene (ISG) products that collectively establish an antiviral state, reining in viral replication and spread [19] . Flaviviruses are known to subject to innate immune control and ZIKV is no exception [20] . It has been recently reported that mice lacking Ifnar1 or triply deficient for Irf3/Irf5/Irf7 supported heightened ZIKV replication, concomitant with developing neurological diseases [21] . Of the~300 known ISGs, IFITM1, IFITM3 and Viperin have been shown to inhibit ZIKV [22, 23] . However, much remains to be learned regarding ZIKV restriction factors-inhibitory host factors against ZIKV, particularly those that are constitutively expressed and whose expression is not or only moderately induced by IFNs.