Language
English
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
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 (
Keywords
Child, Infant, Humans, Child, Preschool, Rotavirus, Diacylglycerol O-Acyltransferase, Virus Replication, Gastroenteritis, Diarrhea, Rotavirus Infections, rotavirus, DGAT1, lipid droplet, viroplasm, proteasome degradation
Published Open-Access
yes
Recommended Citation
Liu, Zheng; Smith, Hunter; Criglar, Jeanette M; et al., "Rotavirus-Mediated DGAT1 Degradation: A Pathophysiological Mechanism of Viral-Induced Malabsorptive Diarrhea" (2023). Faculty and Staff Publications. 1697.
https://digitalcommons.library.tmc.edu/baylor_docs/1697