Evidence map›Paper›PMID 21151776›Full record

ArticlemBio2010

Rotavirus disrupts calcium homeostasis by NSP4 viroporin activity.

Joseph M Hyser, Matthew R Collinson-Pautz, Budi Utama, Mary K Estes

Open access · goldAbstract read
In one paragraph

Article in mBio, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 155 citations in OpenAlex.

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  10. Lab-scale production of postbiotic proteins fromFrontiers in microbiology · 2025
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  14. Host IPmBio · 2024
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  20. Article

26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Joseph M HyserDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
Matthew R Collinson-Pautz
Budi Utama
Mary K Estes
Baylor College of Medicine · USAugustana College · US

Funding

Tissue Analysis & Molecular Imaging CoreP30DK056338 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Geoffrey A Preidis · 2001 to 2026
$28.3M
Research Training in Pediatrics GastroenterolgyT32DK007664 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI DOUGLAS G BURRIN · 1991 to 2026
$8.4M
Regulation of Rotavirus ReplicationR01AI080656 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI Sue Ellen Crawford, Mary Kolb Estes · 2009 to 2026
$7.9M
Training Program in Translational Biology and Molecular MedicineT32GM088129 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI ROONEY, CLIONA M., VAN DEN VEYVER, IGNATIA B · 2010 to 2019
$3.0M
RESEARCH TRAINING PROGRAM IN MOLECULAR VIROLOGYT32AI007471 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI RAMIG, ROBERT FRANKLIN · 1996 to 2010
$2.6M
NIAID NIH HHS R01 AI080656NIAID NIH HHS R01AI080656NIAID NIH HHS T32 AI007471NIAID NIH HHS T32AI007471NIDDK NIH HHS P30 DK056338NIDDK NIH HHS P30DK56338NIDDK NIH HHS T32 DK007664NIDDK NIH HHS T32DK007664NIGMS NIH HHS T32 GM088129
6 · The paper itself

Abstract

Many viruses alter intracellular calcium homeostasis. The rotavirus nonstructural protein 4 (NSP4), an endoplasmic reticulum (ER) transmembrane glycoprotein, increases intracellular levels of cytoplasmic Ca(2+) ([Ca(2+)]cyto) through a phospholipase C-independent pathway, which is required for virus replication and morphogenesis. However, the NSP4 domain and mechanism that increases [Ca(2+)]cyto are unknown. We identified an NSP4 domain (amino acids [aa] 47 to 90) that inserts into membranes and has structural characteristics of viroporins, a class of small hydrophobic viral proteins that disrupt membrane integrity and ion homeostasis to facilitate virus entry, assembly, or release. Mutational analysis showed that NSP4 viroporin activity was mediated by an amphipathic α-helical domain downstream of a conserved lysine cluster. The lysine cluster directed integral membrane insertion of the viroporin domain and was critical for viroporin activity. In epithelial cells, expression of wild-type NSP4 increased the levels of free cytoplasmic Ca(2+) by 3.7-fold, but NSP4 viroporin mutants maintained low levels of [Ca(2+)]cyto, were retained in the ER, and failed to form cytoplasmic vesicular structures, called puncta, which surround viral replication and assembly sites in rotavirus-infected cells. When [Ca(2+)]cyto was increased pharmacologically with thapsigargin, viroporin mutants formed puncta, showing that elevation of calcium levels and puncta formation are distinct functions of NSP4 and indicating that NSP4 directly or indirectly responds to elevated cytoplasmic calcium levels. NSP4 viroporin activity establishes the mechanism for NSP4-mediated elevation of [Ca(2+)]cyto, a critical event that regulates rotavirus replication and virion assembly.

Indexed as

AnimalsCalciumCell LineCytoplasmDNA Mutational AnalysisEndoplasmic ReticulumGlycoproteinsHomeostasisHumansModels, BiologicalModels, ChemicalPorinsProtein Structure, TertiaryRotavirusToxins, BiologicalViral Nonstructural ProteinsCalciumGlycoproteinsNS28 protein, rotavirusPorinsToxins, BiologicalViral Nonstructural ProteinsVirulence Factors

Identifiers

PMID21151776
PMCPMC2999940
OpenAlexW2130963764

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.