Fragile X mental retardation protein is a Zika virus restriction factor that is antagonized by subgenomic flaviviral RNA.

Published online

Journal Article

Subgenomic flaviviral RNA (sfRNA) accumulates during infection due to incomplete degradation of viral genomes and interacts with cellular proteins to promote infection. Here we identify host proteins that bind the Zika virus (ZIKV) sfRNA. We identified fragile X mental retardation protein (FMRP) as a ZIKV sfRNA-binding protein and confirmed this interaction in cultured cells and mouse testes. Depletion of FMRP elevated viral translation and enhanced ZIKV infection, indicating that FMRP is a ZIKV restriction factor. We further observed that an attenuated ZIKV strain compromised for sfRNA production was disproportionately stimulated by FMRP knockdown, suggesting that ZIKV sfRNA antagonizes FMRP activity. Importantly, ZIKV infection and expression of ZIKV sfRNA upregulated endogenous FMRP target genes in cell culture and ZIKV-infected mice. Together, our observations identify FMRP as a ZIKV restriction factor whose activity is antagonized by the sfRNA. Interaction between ZIKV and FMRP has significant implications for the pathogenesis of ZIKV infections.

Full Text

Duke Authors

Cited Authors

  • Soto-Acosta, R; Xie, X; Shan, C; Baker, CK; Shi, P-Y; Rossi, SL; Garcia-Blanco, MA; Bradrick, S

Published Date

  • December 4, 2018

Published In

Volume / Issue

  • 7 /

PubMed ID

  • 30511641

Pubmed Central ID

  • 30511641

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.39023

Language

  • eng

Conference Location

  • England