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

In this study, we demonstrate that TRIM56 exerts a direct antiviral effect on ZIKV infection in human cells of fibroblast-, epithelial-, and neural-origins and that both the E3 ligase activity and C-terminal portion of TRIM56 are critical for restricting ZIKV. Although the C-terminal region of TRIM56 bears sequence homology with the NHL repeat motif of several other TRIM proteins [26] that bind miRNAs and/or mRNAs [27] [28] [29] , we found that the inhibition on ZIKV replication by TRIM56 was not undercut in Dicer-deficient cells, indicative of a miRNA-independent antiviral mechanism. Interestingly, we revealed that TRIM56 was associated with ZIKV RNA in infected cells via its C-terminal portion and such capability was required for its antiviral function. Altogether, our work illustrates that TRIM56 is an intrinsic host restriction factor of ZIKV and shed new lights on the mechanism of action by which this E3 ligase curbs flavivirus replication.