TABLE S1-1: KSHV infection of endothelial cells alters global host cell metabolism. SUPER PATHWAY SUB PATHWAY Glycine, serine and threonine metabolism Alanine and aspartate metabolism Glutamate metabolism Histidine Lysine metabolism Amino Acid Phenylalanine & tyrosine metabolism Tryptophan metabolism Valine, leucine and isoleucine metabolism Cysteine, methionine, SAM, taurine metabolism Urea cycle; arginine-, proline-, metabolism glycine serine N-acetylserine threonine alanine beta-alanine N-acetylalanine aspartate asparagine glutamate glutamine pyroglutamine* gamma-aminobutyrate (GABA) N-acetylglutamate histidine cadaverine lysine 2-aminoadipate N6-acetyllysine phenylalanine GC/MS GC/MS GC/MS GC/MS GC/MS GC/MS LC/MS neg GC/MS GC/MS LC/MS pos LC/MS pos LC/MS pos 48hpi (KSHV vs Mock) 1.37 1.20 1.08 1.19 1.27 1.21 1.02 0.81 1.75 1.10 2.23 0.99 GC/MS 1.21 0.97 LC/MS pos GC/MS GC/MS GC/MS GC/MS LC/MS pos LC/MS pos 0.29 1.07 2.67 1.33 1.16 1.11 1.14 0.34 0.92 1.59 1.18 0.86 1.32 1.13 tyrosine LC/MS pos 1.15 1.21 kynurenine tryptophan C-glycosyltryptophan* isoleucine leucine valine cysteine hypotaurine S-adenosylhomocysteine methionine N-acetylmethionine homocysteine dimethylarginine (SDMA + ADMA) arginine ornithine proline citrulline trans-4-hydroxyproline LC/MS pos LC/MS pos LC/MS pos LC/MS pos LC/MS pos LC/MS pos GC/MS GC/MS LC/MS neg LC/MS pos LC/MS neg GC/MS 6.11 1.13 1.35 1.21 1.29 1.23 1.14 1.18 1.41 1.23 1.08 0.75 31.17 1.03 1.55 1.17 1.21 1.14 0.55 0.97 1.34 1.20 0.93 0.73 LC/MS pos 1.74 1.78 LC/MS pos GC/MS LC/MS pos LC/MS pos GC/MS 1.34 1.41 1.29 2.51 1.68 1.53 1.46 1.18 2.45 1.04 BIOCHEMICAL NAME PLATFORM 96hpi (KSHV vs Mock) 1.08 1.00 0.77 0.98 1.12 0.98 0.69 0.75 1.48 1.18 2.71 1.07 Heat map of statistically significant biochemicals profiled in this study. For paired comparisons, shaded cells indicate p≤0.05 (red indicates that the mean values are significantly higher for that comparison; green values significantly lower). Blue-bolded text indicates 0.05< p< 0.10. TABLE S1-2: KSHV infection of endothelial cells alters global host cell metabolism. SUPER PATHWAY SUB PATHWAY Creatine Polyamine metabolism Amino Acid Glutathione metabolism Dipeptide Peptide Carbohydrate gammaglutamyl Aminosugars metabolism Fructose, mannose, galactose, starch and sucrose metabolism BIOCHEMICAL NAME PLATFORM creatine 5-methylthioadenosine (MTA) putrescine agmatine spermidine spermine glutathione, reduced (GSH) 5-oxoproline glutathione, oxidized (GSSG) cysteine-glutathione disulfide glycylglycine glycylserine glycylproline glycylleucine glycylglutamate aspartylphenylalanine cysteinylglycine gammaglutamylglutamate erythronate* N-acetylneuraminate fructose lactose mannose-6-phosphate LC/MS pos 48hpi (KSHV vs Mock) 1.06 LC/MS pos 0.71 0.90 GC/MS GC/MS LC/MS pos GC/MS 2.76 1.53 2.66 2.94 2.48 1.33 2.97 5.96 LC/MS pos 1.20 0.98 LC/MS neg 1.15 1.10 LC/MS pos 1.21 1.19 LC/MS pos 1.25 1.06 GC/MS GC/MS LC/MS pos LC/MS pos GC/MS LC/MS pos GC/MS 1.34 0.98 0.80 1.09 1.05 1.19 0.89 1.11 0.89 1.02 1.19 0.90 1.22 0.73 LC/MS pos 1.22 1.40 GC/MS GC/MS GC/MS GC/MS GC/MS 0.64 0.92 1.06 0.85 0.75 0.62 1.02 1.13 0.65 3.18 GC/MS 0.43 0.28 sorbitol 96hpi (KSHV vs Mock) 1.00 Heat map of statistically significant biochemicals profiled in this study. For paired comparisons, shaded cells indicate p≤0.05 (red indicates that the mean values are significantly higher for that comparison; green values significantly lower). Blue-bolded text indicates 0.05< p< 0.10. TABLE S1-3: KSHV infection of endothelial cells alters global host cell metabolism. SUPER PATHWAY SUB PATHWAY Glycolysis, gluconeogenesi s, pyruvate metabolism Carbohydrate Nucleotide sugars, pentose metabolism Krebs cycle Energy Oxidative phosphorylation BIOCHEMICAL NAME PLATFORM glycerate glucose-6-phosphate (G6P) glucose 1-phosphate glucose fructose-6-phosphate fructose 1-phosphate Isobar: fructose 1,6diphosphate, glucose 1,6-diphosphate 2-phosphoglycerate 3-phosphoglycerate dihydroxyacetone phosphate (DHAP) phosphoenolpyruvate (PEP) pyruvate lactate 6-phosphogluconate ribitol sedoheptulose-7phosphate gluconate ribose ribose 5-phosphate Isobar: ribulose 5phosphate, xylulose 5phosphate UDP-glucuronate citrate succinate fumarate malate acetylphosphate phosphate pyrophosphate (PPi) GC/MS 48hpi (KSHV vs Mock) 1.55 96hpi (KSHV vs Mock) 1.85 GC/MS 0.64 3.16 GC/MS GC/MS GC/MS GC/MS 1.20 1.38 1.04 1.59 0.33 10.53 2.50 0.93 LC/MS neg 1.21 1.12 GC/MS GC/MS 1.91 1.89 2.05 2.34 GC/MS 1.64 1.50 GC/MS 2.90 4.31 GC/MS GC/MS LC/MS neg GC/MS 1.59 1.18 1.42 0.79 0.98 0.75 3.24 0.73 GC/MS 1.29 1.11 GC/MS GC/MS GC/MS 0.57 1.19 1.65 1.04 1.04 1.09 GC/MS 1.79 1.39 GC/MS GC/MS GC/MS GC/MS GC/MS GC/MS GC/MS GC/MS 1.05 1.00 1.00 1.27 0.97 1.12 1.22 1.48 1.16 1.12 0.86 1.25 0.93 1.28 1.23 1.17 Heat map of statistically significant biochemicals profiled in this study. For paired comparisons, shaded cells indicate p≤0.05 (red indicates that the mean values are significantly higher for that comparison; green values significantly lower). Blue-bolded text indicates 0.05< p< 0.10. TABLE S1-4: KSHV infection of endothelial cells alters global host cell metabolism. SUPER PATHWAY SUB PATHWAY Essential fatty acid Lipid Long chain fatty acid Fatty acid, ester Fatty acid, monohydroxy Fatty acid, dicarboxylate Fatty acid, amide PLATFORM 48hpi (KSHV vs Mock) 96hpi (KSHV vs Mock) LC/MS neg 1.99 3.14 LC/MS neg 1.68 2.63 LC/MS neg 2.15 2.80 LC/MS neg 1.99 2.28 GC/MS GC/MS GC/MS GC/MS 1.34 1.27 0.98 1.26 1.37 1.38 1.12 1.50 GC/MS 1.32 1.02 GC/MS LC/MS neg GC/MS LC/MS neg 1.18 1.57 1.08 1.53 1.31 1.63 1.41 1.58 LC/MS neg 1.55 1.46 GC/MS 1.18 1.57 LC/MS neg 1.67 1.43 LC/MS neg 1.70 1.65 LC/MS neg LC/MS neg GC/MS LC/MS neg LC/MS neg LC/MS neg GC/MS GC/MS GC/MS GC/MS LC/MS neg LC/MS neg 1.38 1.65 1.14 1.65 1.83 1.36 1.29 0.69 0.89 1.08 1.77 1.46 1.23 2.32 1.27 1.22 2.18 2.02 0.99 0.72 1.14 0.48 3.01 2.50 2-hydroxyglutarate GC/MS 1.12 1.04 oleamide GC/MS 1.69 1.71 BIOCHEMICAL NAME dihomo-linolenate (20:3n3 or n6) eicosapentaenoate (EPA; 20:5n3) docosapentaenoate (n3 DPA; 22:5n3) docosahexaenoate (DHA; 22:6n3) myristate (14:0) palmitate (16:0) palmitoleate (16:1n7) margarate (17:0) 10-heptadecenoate (17:1n7) stearate (18:0) oleate (18:1n9) cis-vaccenate (18:1n7) linoleate (18:2n6) 10-nonadecenoate (19:1n9) arachidate (20:0) eicosenoate (20:1n9 or 11) dihomo-linoleate (20:2n6) mead acid (20:3n9) arachidonate (20:4n6) behenate (22:0) docosadienoate (22:2n6) docosatrienoate (22:3n3) adrenate (22:4n6) lignocerate (24:0) hexacosanoate n-Butyl Oleate 4-hydroxybutyrate (GHB) 2-hydroxystearate 2-hydroxypalmitate Heat map of statistically significant biochemicals profiled in this study. For paired comparisons, shaded cells indicate p≤0.05 (red indicates that the mean values are significantly higher for that comparison; green values significantly lower). Blue-bolded text indicates 0.05< p< 0.10. TABLE S1-5: KSHV infection of endothelial cells alters global host cell metabolism. SUPER PATHWAY SUB PATHWAY Glycerolipid metabolism Inositol metabolism Lipid Lysolipid BIOCHEMICAL NAME PLATFORM choline phosphate ethanolamine phosphoethanolamine choline glycerol 3-phosphate (G3P) glycerophosphorylcholine (GPC) cytidine 5'diphosphocholine myo-inositol inositol 1-phosphate (I1P) scyllo-inositol 1palmitoylglycerophospho ethanolamine 2palmitoylglycerophospho ethanolamine* 2palmitoleoylglycerophosp hoethanolamine* 1stearoylglycerophosphoe thanolamine 2oleoylglycerophosphoeth anolamine* 1arachidonoylglycerophos phoethanolamine* 2arachidonoylglycerophos phoethanolamine* 2docosapentaenoylglycer ophosphoethanolamine* 2docosahexaenoylglycero phosphoethanolamine* LC/MS pos GC/MS GC/MS LC/MS pos 48hpi (KSHV vs Mock) 1.39 1.28 1.03 1.23 96hpi (KSHV vs Mock) 1.40 1.06 0.98 1.15 GC/MS 0.54 0.36 LC/MS pos 0.44 0.31 LC/MS pos 1.14 1.06 GC/MS 0.26 1.32 GC/MS 1.23 1.74 GC/MS 1.04 1.19 LC/MS pos 0.95 0.87 LC/MS pos 0.67 0.64 LC/MS pos 0.49 0.48 LC/MS neg 1.38 1.14 LC/MS pos 0.63 0.47 LC/MS neg 1.44 1.81 LC/MS pos 0.65 0.62 LC/MS pos 0.73 0.67 LC/MS pos 0.66 0.53 Heat map of statistically significant biochemicals profiled in this study. For paired comparisons, shaded cells indicate p≤0.05 (red indicates that the mean values are significantly higher for that comparison; green values significantly lower). Blue-bolded text indicates 0.05< p< 0.10. TABLE S1-6: KSHV infection of endothelial cells alters global host cell metabolism. SUPER PATHWAY SUB PATHWAY Lysolipid Lipid Monoacylglycer ol BIOCHEMICAL NAME 1myristoylglycerophospho choline 2myristoylglycerophospho choline* 1palmitoylglycerophospho choline 2palmitoylglycerophospho choline* 1palmitoleoylglycerophosp hocholine* 2palmitoleoylglycerophosp hocholine* 1stearoylglycerophosphoc holine 1oleoylglycerophosphocho line 2oleoylglycerophosphocho line* 2arachidonoylglycerophos phocholine* 2docosapentaenoylglycer ophosphocholine* 1stearoylglycerophosphoi nositol 1arachidonoylglycerophos phoinositol* 1-palmitoylglycerol (1monopalmitin) 1-stearoylglycerol (1monostearin) PLATFORM 48hpi (KSHV vs Mock) 96hpi (KSHV vs Mock) LC/MS pos 0.65 1.06 LC/MS pos 0.97 1.28 LC/MS pos 0.71 0.95 LC/MS pos 0.55 0.94 LC/MS pos 0.59 1.18 LC/MS pos 0.92 0.91 LC/MS pos 0.77 1.02 LC/MS pos 0.73 1.09 LC/MS pos 0.70 0.87 LC/MS pos 0.70 0.84 LC/MS pos 0.87 0.86 LC/MS neg 2.60 4.94 LC/MS neg 1.01 2.56 GC/MS 1.05 1.26 GC/MS 1.13 1.43 Heat map of statistically significant biochemicals profiled in this study. For paired comparisons, shaded cells indicate p≤0.05 (red indicates that the mean values are significantly higher for that comparison; green values significantly lower). Blue-bolded text indicates 0.05< p< 0.10. TABLE S1-7: KSHV infection of endothelial cells alters global host cell metabolism. SUPER PATHWAY SUB PATHWAY Diacylglycerol Sphingolipid Lipid Sterol/Steroid Purine metabolism, (hypo)xanthine / inosine containing Purine metabolism, adenine containing Nucleotide Purine metabolism, guanine containing Purine metabolism, urate metabolism Pyrimidine metabolism, cytidine containing Pyrimidine metabolism, orotate containing Pyrimidine metabolism, uracil containing Purine and pyrimidine metabolism BIOCHEMICAL NAME PLATFORM 1,2-dipalmitoylglycerol sphinganine sphingosine cholesterol 7-dehydrocholesterol 7-betahydroxycholesterol xanthine hypoxanthine GC/MS LC/MS pos LC/MS pos GC/MS GC/MS 48hpi (KSHV vs Mock) 0.57 0.95 1.01 0.85 0.65 96hpi (KSHV vs Mock) 0.99 1.04 1.20 1.00 0.90 GC/MS 1.01 1.82 GC/MS LC/MS neg 1.51 1.39 1.70 1.42 inosine LC/MS neg 1.29 0.75 adenine adenosine adenosine 5'monophosphate (AMP) adenosine 5'diphosphate (ADP) guanine guanosine guanosine 5'monophosphate (GMP) GC/MS LC/MS neg 0.87 0.21 0.84 0.24 LC/MS pos 0.56 0.25 LC/MS neg 0.40 0.31 GC/MS LC/MS neg 3.02 1.11 4.69 0.69 LC/MS pos 0.69 0.89 allantoin GC/MS 0.79 0.99 cytidine 5'monophosphate (5'CMP) LC/MS pos 1.37 0.91 orotate GC/MS 0.56 0.97 uracil uridine uridine 5'monophosphate (UMP) GC/MS LC/MS neg 2.59 1.70 2.57 2.21 LC/MS pos 0.81 0.75 methylphosphate GC/MS 0.92 1.06 Heat map of statistically significant biochemicals profiled in this study. For paired comparisons, shaded cells indicate p≤0.05 (red indicates that the mean values are significantly higher for that comparison; green values significantly lower). Blue-bolded text indicates 0.05< p< 0.10. TABLE S1-8: KSHV infection of endothelial cells alters global host cell metabolism. SUPER PATHWAY SUB PATHWAY Ascorbate and aldarate metabolism Folate metabolism Cofactors and vitamins Nicotinate and nicotinamide metabolism Pantothenate and CoA metabolism Riboflavin metabolism Tocopherol metabolism Chemical Xenobiotics Sugar, sugar substitute, starch ascorbate (Vitamin C) GC/MS 48hpi (KSHV vs Mock) 0.38 threonate GC/MS 0.40 0.51 LC/MS neg 0.88 0.82 LC/MS pos 1.79 1.10 LC/MS pos 0.72 1.05 LC/MS neg 0.65 0.75 LC/MS pos 1.14 1.21 LC/MS pos LC/MS pos 1.59 0.78 1.83 0.94 coenzyme A LC/MS neg 1.50 1.46 flavin adenine dinucleotide (FAD) LC/MS neg 0.98 1.04 GC/MS 0.86 0.86 GC/MS LC/MS neg 0.65 2.10 0.34 2.08 GC/MS 1.09 0.94 BIOCHEMICAL NAME 5-methyltetrahydrofolate (5MeTHF) nicotinamide nicotinamide adenine dinucleotide (NAD+) nicotinamide adenine dinucleotide reduced (NADH) nicotinamide adenine dinucleotide phosphate (NADP+) 1-methylnicotinamide pantothenate alpha-tocopherol glycerol 2-phosphate phenol red erythritol PLATFORM 96hpi (KSHV vs Mock) 0.18 Heat map of statistically significant biochemicals profiled in this study. For paired comparisons, shaded cells indicate p≤0.05 (red indicates that the mean values are significantly higher for that comparison; green values significantly lower). Blue-bolded text indicates 0.05< p< 0.10.