ArticleNature structural & molecular biology2020
Structural basis for STAT2 suppression by flavivirus NS5.
Article in Nature structural & molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- Beyond the Capsid: How Can Post-Translational Modifications Modulate the Multifunctionality of the Orthoflavivirus Capsid Protein?Molecules (Basel, Switzerland) · 2026Review
- NSP1 of Alongshan virus antagonizes type I interferon responses by promoting STUB1-mediated degradation of RIG-I.Cell communication and signaling : CCS · 2026Article
- AI-Assisted Computed Structure Models for Pre-Ubiquitylation Complexes Assembled by Respiratory Syncytial Viral Suppressors of Cellular Interferon Response.International journal of molecular sciences · 2026Article
- Zika virus and host innate immunity: mechanisms of activation and evasion.Frontiers in immunology · 2026Review
- Impact of rare JAK/STAT germline mutations on vaccination-induced innate immune responses in a Tyrolian population.International journal of biological sciences · 2026Article
- An Updated Review of Potential Drug Targets for Japanese Encephalitis.Central nervous system agents in medicinal chemistry · 2026Review
- Coevolutionary constraints of Zika virus nonstructural protein 5 replication and interferon antagonism activities.bioRxiv : the preprint server for biology · 2025Article
- Viral interferon antagonism shapes host tropism.PLoS pathogens · 2025Review
- MARCH6 suppresses Tembusu virus replication by targeting viral NS5 protein for TOLLIP-mediated selective autophagic degradation.Journal of virology · 2025Article
- Structural dynamics of the dengue virus non-structural 5 (NS5) interactions with promoter stem-loop A (SLA).Npj viruses · 2025Article
- Immune pathogenic response landscape of acute posterior multifocal placoid pigment epitheliopathy revealed by scRNA sequencing.Genes and immunity · 2025Article
- Decoding dengue's neurological assault: insights from single-cell CNS analysis in an immunocompromised mouse model.Journal of neuroinflammation · 2025Article
- The segmented flavivirus Alongshan virus reduces mitochondrial mass by degrading STAT2 to suppress the innate immune response.Journal of virology · 2025Article
- Distinct ZIKV strain signatures and type I IFN modulation reveal a protective role of brain endothelial interferon signalingFrontiers in cellular and infection microbiology · 2025Article
- Zika virus NS5 protein inhibits type I interferon signaling via CRL3 E3 ubiquitin ligase-mediated degradation of STAT2.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Flavivirus Non-Structural Protein 5 (NS5): Structure, Functions, and Targeting for Development of Vaccines and Therapeutics.Vaccines · 2024Review
- Evolution of STAT2 resistance to flavivirus NS5 occurred multiple times despite genetic constraints.Nature communications · 2024Article
- Serotype-Specific Regulation of Dengue Virus NS5 Protein Subcellular Localization.ACS infectious diseases · 2024Article
- The Dynamic Relationship between Dengue Virus and the Human Cutaneous Innate Immune Response.Viruses · 2024Review
- The Susceptibility of Chickens to Zika Virus: A Comprehensive Study on Age-Dependent Infection Dynamics and Host Responses.Viruses · 2024Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Suppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of structural information about the viral-cellular complex involved. Here, we report the cryo-EM and crystal structures of human STAT2 (hSTAT2) in complex with the non-structural protein 5 (NS5) of Zika virus (ZIKV) and dengue virus (DENV), revealing two-pronged interactions between NS5 and hSTAT2. First, the NS5 methyltransferase and RNA-dependent RNA polymerase (RdRP) domains form a conserved interdomain cleft harboring the coiled-coil domain of hSTAT2, thus preventing association of hSTAT2 with interferon regulatory factor 9. Second, the NS5 RdRP domain also binds the amino-terminal domain of hSTAT2. Disruption of these ZIKV NS5-hSTAT2 interactions compromised NS5-mediated hSTAT2 degradation and interferon suppression, and viral infection under interferon-competent conditions. Taken together, these results clarify the mechanism underlying the functional antagonism of STAT2 by both ZIKV and DENV.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.