ArticleJournal of virology2013
Activation of the endoplasmic reticulum calcium sensor STIM1 and store-operated calcium entry by rotavirus requires NSP4 viroporin activity.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 76 citations in OpenAlex.
- Review
- A WEEV 6K viroporin activates MLKL-dependent necroptosis to drive inflammatory injury.Cell death discovery · 2026Article
- Targeting virus-interacting host ion channels as a novel antiviral strategy.Acta pharmacologica Sinica · 2026Review
- Human coronavirus 3CL protease manipulates host protein STIM1 to facilitate immune evasion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Fatty acid 2-hydroxylase facilitates rotavirus uncoating and endosomal escape.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- BTP2 restricts Tulane virus and human norovirus replication independent of store-operated calcium entry.Journal of virology · 2025Article
- Viroporin activity is necessary for intercellular calcium signals that contribute to viral pathogenesis.Science advances · 2025Article
- Role of Divalent Cations in Infections in Host-Pathogen Interaction.International journal of molecular sciences · 2024Review
- Decoding mechanisms of diarrhea induction by enteric viruses.PLoS pathogens · 2024Review
- Viral regulation of organelle membrane contact sites.PLoS biology · 2024Article
- Host IPmBio · 2024Article
- Staphylococcus aureus α-toxin impairs early neutrophil localization via electrogenic disruption of store-operated calcium entry.Cell reports · 2023Article
- Targeting host calcium channels and viroporins: a promising strategy for SARS-CoV-2 therapy.Future virology · 2023Review
- Differential Cellular Sensing of Fusion from within and Fusion from without during Virus Infection.Viruses · 2023Article
- Gastrointestinal organoids in the study of viral infections.American journal of physiology. Gastrointestinal and liver physiology · 2023Review
- Re-Examining Rotavirus Innate Immune Evasion: Potential Applications of the Reverse Genetics System.mBio · 2022Review
- Calcium-sensing receptor acts as an antiviral factor for rotavirus infections and participates in cellular antiviral response.Iranian journal of basic medical sciences · 2022Article
- Opposite Effects of Apoptotic and Necroptotic Cellular Pathways on Rotavirus Replication.Journal of virology · 2022Article
- Functions of Viroporins in the Viral Life Cycle and Their Regulation of Host Cell Responses.Frontiers in immunology · 2022Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Rotavirus nonstructural protein 4 (NSP4) induces dramatic changes in cellular calcium homeostasis. These include increased endoplasmic reticulum (ER) permeability, resulting in decreased ER calcium stores and activation of plasma membrane (PM) calcium influx channels, ultimately causing a 2- to 4-fold elevation in cytoplasmic calcium. Elevated cytoplasmic calcium is absolutely required for virus replication, but the underlying mechanisms responsible for calcium influx remain poorly understood. NSP4 is an ER-localized viroporin, whose activity depletes ER calcium, which ultimately leads to calcium influx. We hypothesized that NSP4-mediated depletion of ER calcium activates store-operated calcium entry (SOCE) through activation of the ER calcium sensor stromal interaction molecule 1 (STIM1). We established and used a stable yellow fluorescent protein-expressing STIM1 cell line (YFP-STIM1) as a biosensor to assess STIM1 activation (puncta formation) by rotavirus infection and NSP4 expression. We found that STIM1 is constitutively active in rotavirus-infected cells and that STIM1 puncta colocalize with the PM-localized Orai1 SOCE calcium channel. Expression of wild-type NSP4 activated STIM1, resulting in PM calcium influx, but an NSP4 viroporin mutant failed to induce STIM1 activation and did not activate the PM calcium entry pathway. Finally, knockdown of STIM1 significantly reduced rotavirus yield, indicating STIM1 plays a critical role in virus replication. These data demonstrate that while rotavirus may ultimately activate multiple calcium channels in the PM, calcium influx is predicated on NSP4 viroporin-mediated activation of STIM1 in the ER. This is the first report of viroporin-mediated activation of SOCE, reinforcing NSP4 as a robust model to understand dysregulation of calcium homeostasis during virus infections.
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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.