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

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.