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

ABSTRACT: Human cytomegalovirus (HCMV) modulates cellular metabolism to support productive infection, and the HCMV U_L38 protein drives many aspects of this HCMV-induced metabolic program. However, it remains to be determined whether virally-induced metabolic alterations might induce novel therapeutic vulnerabilities in virally infected cells. Here, we explore how HCMV infection and the U_L38 protein modulate cellular metabolism and how these changes alter the response to nutrient limitation. We find that expression of U_L38, either in the context of HCMV infection or in isolation, sensitizes cells to glucose limitation resulting in cell death. This sensitivity is mediated through U_L38's inactivation of the TSC complex subunit 2 (TSC2) protein, a central meta

SUBMITTER: Raymonda MH 

PROVIDER: S-EPMC10245705 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature