ArticleJournal of virology2025
Dengue and Zika virus NS4B proteins differ in topology and in determinants of ER membrane protein complex dependency.
Article in Journal of virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- SLC3A2 promotes early-stage of Zika virus infection in human placental cells and astrocytes.Infectious diseases & immunity · 2026Article
- West Nile virus and Zika virus infections induce aggresome formation in human neural progenitor and A549 cells.Journal of virology · 2026Article
- Discovery of a potent anti-Zika virus benzamide series targeting the viral protein NS4B.PLoS pathogens · 2026Article
- Zika NS2B Protein: In Vitro Formation of Large Multimeric Networks.International journal of molecular sciences · 2026Article
- Meta-analysis of functional genomics studies reveals conserved cellular pathways required by viruses of pandemic concern.Access microbiology · 2026Article
- Zika virus and host protein interactions for understanding molecular mechanisms of pathogenesis and therapeutic development.Frontiers in cellular and infection microbiology · 2026Review
- AlphaFold Prediction of Protein-Protein Interactions in theInternational journal of molecular sciences · 2025Article
- Discovery of a potent anti-Zika virus benzamide series targeting the viral protein NS4B.bioRxiv : the preprint server for biology · 2025Article
- Deciphering the membrane topology of the pestiviral non-structural protein 4B (NS4B).Journal of virology · 2025Article
- Functional Roles and Host Interactions ofPathogens (Basel, Switzerland) · 2025Review
- Structural elucidation of Langat virus helicase unveils dual-target inhibition for broad-spectrum anti-flaviviruses strategy.Frontiers in cellular and infection microbiology · 2025Article
- Flavivirus NS4B proteins do not form homodimers: discrepancies with an AlphaFold-based oligomeric model.Computational and structural biotechnology journal · 2025Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Flaviviruses utilize the cellular endoplasmic reticulum (ER) for all aspects of their lifecycle. Genome replication and other viral activities take place in structures called replication organelles (ROs), which are invaginations induced in the ER membrane. Among the required elements for RO formation is the biogenesis of viral nonstructural proteins NS4A and NS4B. We have previously shown that NS4A and NS4B from Dengue virus (DENV) and Zika virus (ZIKV) depend on the cellular ER membrane protein complex (EMC) for biogenesis. Here, we find that this dependency extends to the NS4A and NS4B proteins of Yellow Fever virus (YFV) and West Nile virus (WNV), which share similar computationally predicted membrane topologies. However, we demonstrate that ZIKV NS4B has different determinants of its dependency on the EMC than those for DENV NS4B, as well as a different membrane topology. Furthermore, we characterize mutant isolates of DENV and ZIKV that were serially passaged in EMC knockout cells and find that none are completely independent of the EMC for infection, and that mutant NS4B proteins remain sensitive to EMC depletion, suggesting a high genetic barrier to EMC depletion. Collectively, our findings are consistent with a model in which the EMC recognizes multiple determinants in the NS4B protein to support infection in several flaviviruses of critical public health importance.IMPORTANCEThe NS4A and NS4B proteins of flaviviruses are critically important to replication, but little is known about their function. It has been previously reported that the cellular EMC supports the biogenesis of NS4A and NS4B from Dengue and Zika virus. In this work, we demonstrate that this dependency on the EMC for NS4A and NS4B biogenesis extends to the West Nile and Yellow Fever viruses. Furthermore, we examine the features of ZIKV NS4B and find that its membrane topology of ZIKV NS4B and its determinants of dependency on the EMC are different from those previously described in DENV NS4B. Finally, we present evidence that there is a high genetic barrier for Dengue and Zika viruses to overcome EMC depletion.
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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 Socratic graph.