ArticleJournal of virology1998
Mutations in rotavirus nonstructural glycoprotein NSP4 are associated with altered virus virulence.
Article in Journal of virology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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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.
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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
46 citing papers in PubMed, 139 citations in OpenAlex.
- Treatment of rotaviral gastroenteritis with Qiwei Baizhu powder.World journal of gastroenterology · 2001Trial
- Maternal Immunization with VP8* mRNA Vaccine Yields Superior Passive Transfer of Rotavirus-Neutralizing Antibodies to Foals.Vaccines · 2026Article
- Swine Group A rotavirus vaccines: current status, adjuvant strategies, challenges, and future perspectives.Frontiers in veterinary science · 2026Review
- Viroporin activity is necessary for intercellular calcium signals that contribute to viral pathogenesis.Science advances · 2025Article
- Genomic analysis of DS-1-like human rotavirus A strains uncovers genetic relatedness of NSP4 gene with animal strains in Manhiça District, Southern Mozambique.Scientific reports · 2024Article
- Article
- Rotavirus Calcium Dysregulation Manifests as Dynamic Calcium Signaling in the Cytoplasm and Endoplasmic Reticulum.Scientific reports · 2019Article
- Analysis of structure-function relationship in porcine rotavirus A enterotoxin gene.Journal of veterinary science · 2018Article
- Group A Rotavirus Associated with Encephalitis in Red Fox.Emerging infectious diseases · 2017Article
- Designing, Construction and Expression of a Recombinant Fusion Protein Comprising the Hepatitis E Virus ORF2 and Rotavirus NSP4 in the Baculovirus Expression System.Jundishapur journal of microbiology · 2016Article
- Rotavirus and Serotonin Cross-Talk in Diarrhoea.PloS one · 2016Article
- Comparative analysis of pentavalent rotavirus vaccine strains and G8 rotaviruses identified during vaccine trial in Africa.Scientific reports · 2015Article
- Whole-genome analyses of DS-1-like human G2P[4] and G8P[4] rotavirus strains from Eastern, Western and Southern Africa.Virus genes · 2014Article
- Absence of genetic differences among G10P[11] rotaviruses associated with asymptomatic and symptomatic neonatal infections in Vellore, India.Journal of virology · 2014Article
- Virulence-associated genome mutations of murine rotavirus identified by alternating serial passages in mice and cell cultures.Journal of virology · 2014Article
- Mutational analysis of the rotavirus NSP4 enterotoxic domain that binds to caveolin-1.Virology journal · 2013Article
- Human G9P[8] rotavirus strains circulating in Cameroon, 1999-2000: Genetic relationships with other G9 strains and detection of a new G9 subtype.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2013Article
- Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes.Diabetologia · 2013Article
- Genetic divergence of rotavirus nonstructural protein 4 results in distinct serogroup-specific viroporin activity and intracellular punctate structure morphologies.Journal of virology · 2012Article
- Clinical and molecular observations of two fatal cases of rotavirus-associated enteritis in children in Italy.Journal of clinical microbiology · 2011Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Rotaviruses are major pathogens causing life-threatening dehydrating gastroenteritis in children and animals. One of the nonstructural proteins, NSP4 (encoded by gene 10), is a transmembrane, endoplasmic reticulum-specific glycoprotein. Recently, our laboratory has shown that NSP4 causes diarrhea in 6- to 10-day-old mice by functioning as an enterotoxin. To confirm the role of NSP4 in rotavirus pathogenesis, we sequenced gene 10 from two pairs of virulent and attenuated porcine rotaviruses, the OSU and Gottfried strains. Comparisons of the NSP4 sequences from these two pairs of rotaviruses suggested that structural changes between amino acids (aa) 131 and 140 are important in pathogenesis. We next expressed the cloned gene 10 from the OSU virulent (OSU-v) and OSU attenuated (OSU-a) viruses by using the baculovirus expression system and compared the biological activities of the purified proteins. NSP4 from OSU-v virus increased intracellular calcium levels over 10-fold in intestinal cells when added exogenously and 6-fold in insect cells when expressed endogenously, whereas NSP4 from OSU-a virus had little effect. NSP4 from OSU-v caused diarrhea in 13 of 23 neonatal mice, while NSP4 from OSU-a caused disease in only 4 of 25 mice (P < 0.01). These results suggest that avirulence is associated with mutations in NSP4. Results from site-directed mutational analyses showed that mutated OSU-v NSP4 with deletion or substitutions in the region of aa 131 to 140 lost its ability to increase intracellular calcium levels and to induce diarrhea in neonatal mice, confirming the importance of amino acid changes from OSU-v NSP4 to OSU-a NSP4 in the alteration of virus virulence.
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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.