TY - JOUR
T1 - Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism
AU - Vastag, Livia
AU - Koyuncu, Emre
AU - Grady, Sarah L.
AU - Shenk, Thomas E.
AU - Rabinowitz, Joshua D.
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79960958455&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960958455&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1002124
DO - 10.1371/journal.ppat.1002124
M3 - Article
C2 - 21779165
AN - SCOPUS:79960958455
SN - 1553-7366
VL - 7
JO - PLoS pathogens
JF - PLoS pathogens
IS - 7
M1 - e1002124
ER -