ArticleProceedings of the National Academy of Sciences of the United States of America2022
The RNA polymerase of cytoplasmically replicating Zika virus binds with chromatin DNA in nuclei and regulates host gene transcription.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 16 citations in OpenAlex.
- Nuclear activities and interactome of the NS5 protein of tick-borne encephalitis virus.Journal of virology · 2026Article
- Review
- Virus-host interactome reveals host cellular pathways perturbed by tick-borne encephalitis virus infection.iScience · 2026Article
- Zika virus: unraveling the complex interplay between viral pathogenesis and host immune defenses.Virology journal · 2026Review
- Nuclear activities and interactome of the NS5 protein of Tick-Borne Encephalitis Virus.bioRxiv : the preprint server for biology · 2026Article
- Zika virus and host protein interactions for understanding molecular mechanisms of pathogenesis and therapeutic development.Frontiers in cellular and infection microbiology · 2026Review
- Innexin DNA-binding domains regulateiScience · 2025Article
- Yellow Fever Virus Interactomes Reveal Common and Divergent Strategies of Replication and Evolution for Mosquito-borne Flaviviruses.bioRxiv : the preprint server for biology · 2025Article
- Label-free nanoscopy of cell metabolism by ultrasensitive reweighted visible stimulated Raman scattering.Nature methods · 2025Article
- Zika and dengue viruses differentially modulate host mRNA processing factors defining its virulence.NAR molecular medicine · 2025Article
- Erp57 facilitates ZIKV-induced DNA damage via NS2B/NS3 complex formation.Emerging microbes & infections · 2024Article
- Review
- The Flavivirus Non-Structural Protein 5 (NS5): Structure, Functions, and Targeting for Development of Vaccines and Therapeutics.Vaccines · 2024Review
- A Zika virus protein expression screen in Drosophila to investigate targeted host pathways during development.Disease models & mechanisms · 2024Article
- Review
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 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.
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