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, an E3 ubiquitin ligase ubiquitously expressed in human tissues [25] , poses a barrier to ZIKV infection in human cells. Ectopic expression of TRIM56 inhibited ZIKV propagation, while depletion of endogenous TRIM56 had the opposite effect. Importantly, this was demonstrated in cells of fibroblast, epithelial and neural origins, representative cell types targeted by ZIKV in vivo. No less important, we confirmed that TRIM56 restricts both African and Asian lineages of ZIKVs. To our knowledge, this is the first study that identifies a host restriction factor of ZIKV in the TRIM protein family. Taken into account the neurotropism of ZIKV infection in vivo, our revelations that TRIM56 was basally expressed in human brain [25] , human astrocytes SVGA and primary mouse neurons (this study) and that its expression was elevated following ZIKV infection in neural cell types support the biological relevance of TRIM56 as a host restriction factor of ZIKV. In agreement with our previous observation [25] , TRIM56 abundance was only moderately upregulated by coli were separated on SDS-PAGE, followed by Coomassie blue staining (left) and immunoblotting (right), respectively. Results were representative of three independent experiments. Solid circles denote degradation products of MBP-TRIM56-C392. (D and E) Two micrograms of MBP-polylinker or MBP-T56-C392 protein was incubated with 0.5 μg of ZIKV RNA at room temperature for 30 min, followed by pull-down of MBP-tagged proteins using amylose resin. After washing procedure, specifically bound proteins (D) and viral RNA (E) in pull-down complex were analyzed by immunoblotting (D) and qPCR (E), respectively. Student t-test, �� P<0.01, ��� P<0.001. Results were reproduced three times.