Rotavirus is a major cause of severe gastroenteritis among very young children. In developing countries, rotavirus is the major cause of mortality in children under five years old, causing up to 20% of all childhood deaths in countries with high diarrheal disease burden, with more than 90% of these deaths occurring in Africa and Asia. Rotavirus vaccination mimics the first infection without causing illness, thus inducing strong and broad heterotypic immunity against prospective rotavirus infections. Two live vaccines are available, Rotarix and RotaTeq, but vaccination efforts are hampered by high production costs. Here, we present a dataset containing a genome-wide RNA interference (RNAi) screen that identified silencing events that enhanced rotavirus replication. Evaluated against several rotavirus vaccine strains, hits were validated in a Vero vaccine cell line as well as CRISPR/Cas9 generated cells permanently and stably lacking the genes that affect RV replication. Knockout cells were dramatically more permissive to RV replication and permitted an increase in rotavirus replication. These data show a means to improve manufacturing of rotavirus vaccine.
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http://dx.doi.org/10.1038/sdata.2017.21 | DOI Listing |
Front Public Health
January 2025
Bavarian Health and Food Safety Authority (LGL), Munich, Germany.
[This corrects the article DOI: 10.3389/fpubh.2024.
View Article and Find Full Text PDFNat Commun
January 2025
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, PR China.
Broadly neutralizing antibodies (bNAbs) could offer escape-tolerant and lasting protection against viral infections and therefore guide development of broad-spectrum vaccines. The increasing challenge posed by viral evolution and immune evasion intensifies the importance of the discovery of bNAbs and their underlying neutralization mechanism. Here, focusing on the pivotal viral protein VP4 of rotavirus (RV), we identify a potent bNAb, 7H13, exhibiting broad-spectrum neutralization across diverse RV genotypes and demonstrating strong prevention of virus infection in female mice.
View Article and Find Full Text PDFGut Pathog
January 2025
Diarrheal Pathogens Research Unit (DPRU), Department of Virology, Sefako Makgatho Health Sciences University, Ga-rankuwa, Pretoria, South Africa.
Bacterial flagellin, a potent intestinal innate immune activator, prevents murine rotavirus (RV) infection independent of adaptive immunity and interferons. The flagellin-induced immunity is mediated by Toll-like receptor (TLR5) and Nod-like receptor C4 (NLRC4), which elicit the production of interleukins 22 (IL-22) and IL-18, respectively. Here, we assessed whether a high abundance of flagellin at the time of vaccination would negatively affect the oral RV vaccine take.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Viruses engage in a variety of processes to subvert host defenses and create an environment amenable to replication. Here, using rotavirus as a prototype, we show that calcium conductance out of the endoplasmic reticulum by the virus encoded ion channel, , induces intercellular calcium waves that extend beyond the infected cell and contribute to pathogenesis. Viruses that lack the ability to induce this signaling show diminished viral shedding and attenuated disease in a mouse model of rotavirus diarrhea.
View Article and Find Full Text PDFTissue Cell
December 2024
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address:
Rotavirus is the most important cause of severe gastroenteritis in infants and children worldwide. This virus causes an increase in inflammatory responses by increasing cellular oxidative stress and the expression and activity of the transcription factor NF-κB and COX-2. As a result of NF-κB activation, the expression of inflammatory cytokines also increases.
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