ArticlePLoS pathogens2015
Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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
31 citing papers in PubMed, 60 citations in OpenAlex.
- Targeting virus-interacting host ion channels as a novel antiviral strategy.Acta pharmacologica Sinica · 2026Review
- A novel antiviral strategy by disrupting the equilibrium of virus-host calcium homeostasis.Current opinion in virology · 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
- Shaping Viral Infection Outcomes via Organelle Remodeling.Annual review of virology · 2025Review
- Article
- The crucial role of intercellular calcium wave propagation triggered by influenza A virus in promoting infection.Cell communication and signaling : CCS · 2025Article
- Flunarizine as a Candidate for Drug Repurposing Against Human Pathogenic Mammarenaviruses.Viruses · 2025Article
- Viral regulation of organelle membrane contact sites.PLoS biology · 2024Article
- Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder.International journal of molecular sciences · 2023Review
- Calcium Influx Regulates the Replication of Several Negative-Strand RNA Viruses Including Severe Fever with Thrombocytopenia Syndrome Virus.Journal of virology · 2023Article
- Hypocalcemia is associated with adverse outcomes in patients hospitalized with COVID-19.Endocrine · 2023Article
- Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding.EMBO reports · 2022Article
- Article
- The ins and outs of virus trafficking through acidic CaCell calcium · 2022Review
- Could Lower Testosterone in Older Men Explain Higher COVID-19 Morbidity and Mortalities?International journal of molecular sciences · 2022Review
- Calcium Ions Signaling: Targets for Attack and Utilization by Viruses.Frontiers in microbiology · 2022Review
- Dysregulation of host cell calcium signaling during viral infections: Emerging paradigm with high clinical relevance.Molecular aspects of medicine · 2021Review
- Lipid-protein interactions in virus assembly and budding from the host cell plasma membrane.Biochemical Society transactions · 2021Review
- Compound FC-10696 Inhibits Egress of Marburg Virus.Antimicrobial agents and chemotherapy · 2021Article
- Endoplasmic reticulum & mitochondrial calcium homeostasis: The interplay with viruses.Mitochondrion · 2021Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Hemorrhagic fever viruses, including the filoviruses (Ebola and Marburg) and arenaviruses (Lassa and Junín viruses), are serious human pathogens for which there are currently no FDA approved therapeutics or vaccines. Importantly, transmission of these viruses, and specifically late steps of budding, critically depend upon host cell machinery. Consequently, strategies which target these mechanisms represent potential targets for broad spectrum host oriented therapeutics. An important cellular signal implicated previously in EBOV budding is calcium. Indeed, host cell calcium signals are increasingly being recognized to play a role in steps of entry, replication, and transmission for a range of viruses, but if and how filoviruses and arenaviruses mobilize calcium and the precise stage of virus transmission regulated by calcium have not been defined. Here we demonstrate that expression of matrix proteins from both filoviruses and arenaviruses triggers an increase in host cytoplasmic Ca2+ concentration by a mechanism that requires host Orai1 channels. Furthermore, we demonstrate that Orai1 regulates both VLP and infectious filovirus and arenavirus production and spread. Notably, suppression of the protein that triggers Orai activation (Stromal Interaction Molecule 1, STIM1) and genetic inactivation or pharmacological blockade of Orai1 channels inhibits VLP and infectious virus egress. These findings are highly significant as they expand our understanding of host mechanisms that may broadly control enveloped RNA virus budding, and they establish Orai and STIM1 as novel targets for broad-spectrum host-oriented therapeutics to combat these emerging BSL-4 pathogens and potentially other enveloped RNA viruses that bud via similar mechanisms.
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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.