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

Ping Li, Junyu Wu, Shujie Liu, Ruiqing Lu, Hualian Jiang, Niu Wang, Manhui Luo, Liping Guo, Jingshu Xiao, Lang Bu, Lihong Liu, Fan Xing, Hong Peng, Chunmei Li, Lan Ma, Bo Zhao, Zhongwei Zhou, Deyin Guo

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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 neurogenesis. Mechanistically, ZIKV NS5 binds onto the gene body of its target genes and then blocks their transcriptional elongation. The utero electroporation in pregnant mice showed that NS5 expression significantly disrupts the neurogenesis by reducing the number of Sox2- and Tbr2-positive cells in the fetal cortex. Together, our findings demonstrate a molecular clue linking to the abnormal neurodevelopment caused by ZIKV infection and also provide intriguing insights into the interaction between the host cell and the pathogenic RNA virus, where the cytoplasmic RNA virus encodes a DNA-binding protein to control the transcription of host cell in the nuclei.

Original languageEnglish (US)
Article numbere2205013119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number49
StatePublished - Dec 6 2022


  • DNA binding
  • Zika virus
  • human neural progenitor cells (hNPCs)
  • nonstructural protein 5 (NS5)
  • transcriptional elongation

ASJC Scopus subject areas

  • General


Dive into the research topics of 'The RNA polymerase of cytoplasmically replicating Zika virus binds with chromatin DNA in nuclei and regulates host gene transcription'. Together they form a unique fingerprint.

Cite this