Cytomegalovirus-mediated activation of pyrimidine biosynthesis drives UDP-sugar synthesis to support viral protein glycosylation.

ABSTRACT: Human cytomegalovirus (HCMV) induces numerous changes to the host metabolic network that are critical for high-titer viral replication. We find that HCMV infection substantially induces de novo pyrimidine biosynthetic flux. This activation is important for HCMV replication because inhibition of pyrimidine biosynthetic enzymes substantially decreases the production of infectious virus, which can be rescued through medium supplementation with pyrimidine biosynthetic intermediates. Metabolomic analysis revealed that pyrimidine biosynthetic inhibition considerably reduces the levels of various UDP-sugar metabolites in HCMV-infected, but not mock-infected, cells. Further, UDP-sugar biosynthesis, which provides the sugar substrates required for glycosylation reactions, was found to be induced du

SUBMITTER: DeVito SR 

PROVIDER: S-EPMC4273352 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature