Dataset Information
Cytomegalovirus-induced inactivation of TSC2 disrupts the coupling of fatty acid biosynthesis to glucose availability resulting in a vulnerability to glucose starvation.
Ontology highlight
ABSTRACT: Importance
Viruses modulate host cell metabolism to support the mass production of viral progeny. For human cytomegalovirus, we find that the viral UL38 protein is critical for driving these pro-viral metabolic changes. However, our results indicate that these changes come at a cost, as UL38 induces an anabolic rigidity that leads to a metabolic vulnerability. We find that UL38 decouples the link between glucose availability and fatty acid biosynthetic activity. Normal cells respond to glucose limitation by down-regulating fatty acid biosynthesis. Expression of UL38 results in the inability to modulate fatty acid biosynthesis in response to glucose limitation, which results in cell death. We find this vulnerability in the context of viral infection, but this linkage between fatty acid biosynthesis, glucose availability, and cell death could have broader implications in other contexts or pathologies that rely on glycolytic remodeling, for example, oncogenesis.
SUBMITTER: Raymonda MH
PROVIDER: S-EPMC10790783 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Publications
Cytomegalovirus-induced inactivation of TSC2 disrupts the coupling of fatty acid biosynthesis to glucose availability resulting in a vulnerability to glucose starvation.
mBio 20231220 1
<h4>Importance</h4>Viruses modulate host cell metabolism to support the mass production of viral progeny. For human cytomegalovirus, we find that the viral U<sub>L</sub>38 protein is critical for driving these pro-viral metabolic changes. However, our results indicate that these changes come at a cost, as U<sub>L</sub>38 induces an anabolic rigidity that leads to a metabolic vulnerability. We find that U<sub>L</sub>38 decouples the link between glucose availability and fatty acid biosynthetic ac ...[more]
