Figure 1.

MYXV infection alters the Arg biosynthetic pathway: B16F10 tumors established in C57BL/6J mice were treated with either PBS or MyxGFP. Four days post treatment, tumors were harvested and immediately snap-frozen in liquid nitrogen. Whole-tumor homogenates were then used to quantify a set of 226-metabolite species via LC-MS (n=5–7 tumors per group). (A) Metabolite set enrichment analysis of LC-MS results. (B) Viral yields from B16F10 cells grown in DMEM lacking various single amino acids for 24 hours and infected with MyxGFP at an multiplicity of infection (MOI)=5. Cells were harvested 24 hours post infection for viral quantification. (C) Heatmap of metabolite concentrations involved in the urea cycle and polyamine biosynthesis from experiment (A). Color indicates –log₁₀(Holm adjusted p value). Arrows indicate significant (Holm adjusted p value <0.05) increases or decreases in MyxGFP-treated cohort relative to mock cohort. Gray indicates species not evaluated in this panel. Arg, arginine; ASL, argininosuccinate lyase; DMEM, Dulbecco’s Modified Eagle Medium; FFU, focus-forming unit; LC-MS, iquid chromatography–mass spectrometry; MyxGFP, myxoma virus-expressing green fluorescent protein; MYXV, myxoma virus; PBS, phosphate-buffered saline; ODC, ornithine decarboxylase; SRM, spermidine synthase; SMS, spermine synthase; SMOX, spermine oxidase.