Cytomegalovirus-induced inactivation of TSC2 disrupts the coupling of fatty acid biosynthesis to glucose availability resulting in a vulnerability to glucose starvation.

ABSTRACT:

Importance

Viruses modulate host cell metabolism to support the mass production of viral progeny. For human cytomegalovirus, we find that the viral U_L38 protein is critical for driving these pro-viral metabolic changes. However, our results indicate that these changes come at a cost, as U_L38 induces an anabolic rigidity that leads to a metabolic vulnerability. We find that U_L38 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 U_L38 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

SUBMITTER: Raymonda MH 

PROVIDER: S-EPMC10790783 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature