Divergent Effects of Human Cytomegalovirus and Herpes Simplex Virus-1 on Cellular Metabolism

PLoS Pathogens

Joshua D. Rabinowitz¹  Livia Vastag¹  Emre Koyuncu²  Sarah L. Grady²  Thomas E. Shenk² 

[1] Department of Chemistry, Princeton University, Princeton, New Jersey, United States of America;Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America

关键词: Cell metabolism;    Host cells;    Drug metabolism;    Citric acid cycle;    Fibroblasts;    Pyruvate;    Enzyme metabolism;    Glucose metabolism;   

DOI  :  10.1371/journal.ppat.1002124

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Viruses rely on the metabolic network of the host cell to provide energy and macromolecular precursors to fuel viral replication. Here we used mass spectrometry to examine the impact of two related herpesviruses, human cytomegalovirus (HCMV) and herpes simplex virus type-1 (HSV-1), on the metabolism of fibroblast and epithelial host cells. Each virus triggered strong metabolic changes that were conserved across different host cell types. The metabolic effects of the two viruses were, however, largely distinct. HCMV but not HSV-1 increased glycolytic flux. HCMV profoundly increased TCA compound levels and flow of two carbon units required for TCA cycle turning and fatty acid synthesis. HSV-1 increased anapleurotic influx to the TCA cycle through pyruvate carboxylase, feeding pyrimidine biosynthesis. Thus, these two related herpesviruses drive diverse host cells to execute distinct, virus-specific metabolic programs. Current drugs target nucleotide metabolism for treatment of both viruses. Although our results confirm that this is a robust target for HSV-1, therapeutic interventions at other points in metabolism might prove more effective for treatment of HCMV.

【 授权许可】

CC BY