Human adenovirus serotype 5 infection dysregulates cysteine, purine, and unsaturated fatty acid metabolism in fibroblasts

<p>Viral infection causes cellular dysregulation of metabolic chemical reactions. Viruses alter host metabolism for their replication needs. How viruses impact specific metabolic pathways is not well-understood, even in a well-studied virus like human adenovirus. Adenoviral infection is known to influence cellular glycolysis and respiration, however, global effects on overall cellular metabolism in response to infection are unclear. Further, few studies have employed an untargeted approach, combining emphasis on viral dosage and of infection. To address this, we employed untargeted metabolomics to quantify the dynamic metabolic shifts in fibroblasts infected with human adenovirus serotype 5 (HAdV-5) at 3 dosages (0.5, 1.0, and 2.0 multiplicity of infection [MOI]) and across 4 time points (6, 12, 24, and 36 hours post-infection [HPI]). The greatest differences in individual metabolites were observed at 6- and 12-hours post-infection, correlating to the early phase of the HAdV-5 infection cycle. In addition to effects on glycolysis and respiration, adenoviral infection downregulated cysteine and unsaturated fatty acid metabolism, while upregulating aspects of purine metabolism. These results reveal specific metabolic pathways dysregulated by adenoviral infection and the associated, dynamic shifts in metabolism suggesting that viral infections alter energetics via profound changes in lipid, nucleic acid, and protein metabolism. The results reveal previously unconsidered metabolic pathways disrupted by HAdV-5 that can alter cellular metabolism, thereby prompting further investigation into HAdV mechanisms and antiviral targeting.</p>