ArticleJournal of virology2020
NS5 Sumoylation Directs Nuclear Responses That Permit Zika Virus To Persistently Infect Human Brain Microvascular Endothelial Cells.
Article in Journal of virology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- SUMOylation of pseudorabies virus thymidine kinase regulates its nuclear localization and facilitates neuronal replication and reactivation.PLoS pathogens · 2026Article
- Article
- Zika virus and host protein interactions for understanding molecular mechanisms of pathogenesis and therapeutic development.Frontiers in cellular and infection microbiology · 2026Review
- Pathogenicity and virulence of Powassan virus.Virulence · 2025Review
- ZNF33B facilitates Japanese encephalitis virus replication by controlling HSPB1/8-mediated SUMOylation of nonstructural protein 5.Journal of virology · 2025Article
- Unraveling the complexities of neurotropic virus infection and immune evasion.Microbiology and molecular biology reviews : MMBR · 2025Review
- Article
- Pathogen-induced hijacking of host SUMOylation: from molecular mechanisms and prospects for therapeutic modulation.Frontiers in immunology · 2025Review
- Distinct ZIKV strain signatures and type I IFN modulation reveal a protective role of brain endothelial interferon signalingFrontiers in cellular and infection microbiology · 2025Article
- E2 Ubiquitin-Conjugating Enzymes Regulates Dengue Virus-2 Replication inMicroorganisms · 2024Article
- Balancing acts: The posttranslational modification tightrope of flavivirus replication.PLoS pathogens · 2024Review
- Age-dependent Powassan virus lethality is linked to glial cell activation and divergent neuroinflammatory cytokine responses in a murine model.Journal of virology · 2024Article
- TRIMming down Flavivirus Infections.Viruses · 2024Review
- Serotype-Specific Regulation of Dengue Virus NS5 Protein Subcellular Localization.ACS infectious diseases · 2024Article
- Article
- Residue K28 of Zika Virus NS5 Protein Is Implicated in Virus Replication and Antagonism of STAT2.Microorganisms · 2024Article
- A Zika virus protein expression screen in Drosophila to investigate targeted host pathways during development.Disease models & mechanisms · 2024Article
- Suppression of TRIM19 by arterivirus nonstructural protein 1 promotes viral replication.Virus research · 2024Article
- The Dynamic Landscape of Capsid Proteins and Viral RNA Interactions in Flavivirus Genome Packaging and Virus Assembly.Pathogens (Basel, Switzerland) · 2024Review
- TRIM28-mediated nucleocapsid protein SUMOylation enhances SARS-CoV-2 virulence.Nature communications · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Zika virus (ZIKV) is cytopathic to neurons and persistently infects brain microvascular endothelial cells (hBMECs), which normally restrict viral access to neurons. Despite replicating in the cytoplasm, ZIKV and Dengue virus (DENV) polymerases, NS5 proteins, are predominantly trafficked to the nucleus. We found that a SUMO interaction motif in ZIKV and DENV NS5 proteins directs nuclear localization. However, ZIKV NS5 formed discrete punctate nuclear bodies (NBs), while DENV NS5 was uniformly dispersed in the nucleoplasm. Yet, mutating one DENV NS5 SUMO site (K546R) localized the NS5 mutant to discrete NBs, and NBs formed by the ZIKV NS5 SUMO mutant (K252R) were restructured into discrete protein complexes. In hBMECs, NBs formed by STAT2 and promyelocytic leukemia (PML) protein are present constitutively and enhance innate immunity. During ZIKV infection or NS5 expression, we found that ZIKV NS5 evicts PML from STAT2 NBs, forming NS5/STAT2 NBs that dramatically reduce PML expression in hBMECs and inhibit the transcription of interferon-stimulated genes (ISG). Expressing the ZIKV NS5 SUMO site mutant (K252R) resulted in NS5/STAT2/PML NBs that failed to degrade PML, reduce STAT2 expression, or inhibit ISG induction. Additionally, the K252 SUMOylation site and NS5 nuclear localization were required for ZIKV NS5 to regulate hBMEC cell cycle transcriptional responses. Our data reveal NS5 SUMO motifs as novel NB coordinating factors that distinguish flavivirus NS5 proteins. These findings establish SUMOylation of ZIKV NS5 as critical in the regulation of antiviral ISG and cell cycle responses that permit ZIKV to persistently infect hBMECs.
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Registered trials
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.