Publication Date
12-19-2023
Journal
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.2302161120
PMID
38079544
PMCID
PMC10743370
PubMedCentral® Posted Date
12-11-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Child, Infant, Humans, Child, Preschool, Rotavirus, Diacylglycerol O-Acyltransferase, Virus Replication, Gastroenteritis, Diarrhea, Rotavirus Infections, rotavirus, DGAT1, lipid droplet, viroplasm, proteasome degradation
Abstract
Gastroenteritis is among the leading causes of mortality globally in infants and young children, with rotavirus (RV) causing ~258 million episodes of diarrhea and ~128,000 deaths annually in infants and children. RV-induced mechanisms that result in diarrhea are not completely understood, but malabsorption is a contributing factor. RV alters cellular lipid metabolism by inducing lipid droplet (LD) formation as a platform for replication factories named viroplasms. A link between LD formation and gastroenteritis has not been identified. We found that diacylglycerol O-acyltransferase 1 (DGAT1), the terminal step in triacylglycerol synthesis required for LD biogenesis, is degraded in RV-infected cells by a proteasome-mediated mechanism. RV-infected DGAT1-silenced cells show earlier and increased numbers of LD-associated viroplasms per cell that translate into a fourfold-to-fivefold increase in viral yield (
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