The RNA polymerase of cytoplasmically replicating Zika virus binds with chromatin DNA in nuclei and regulates host gene transcription.

ABSTRACT: Zika virus (ZIKV) targets the neural progenitor cells (NPCs) in brain during intrauterine infections and consequently causes severe neurological disorders, such as microcephaly in neonates. Although replicating in the cytoplasm, ZIKV dysregulates the expression of thousands of host genes, yet the detailed mechanism remains elusive. Herein, we report that ZIKV encodes a unique DNA-binding protein to regulate host gene transcription in the nucleus. We found that ZIKV NS5, the viral RNA polymerase, associates tightly with host chromatin DNA through its methyltransferase domain and this interaction could be specifically blocked by GTP. Further study showed that expression of ZIKV NS5 in human NPCs markedly suppressed the transcription of its target genes, especially the genes involved in neuro

SUBMITTER: Li P 

PROVIDER: S-EPMC9894162 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature