Human Cytomegalovirus Infection Reduces an Endogenous Antiviral Fatty Acid by Promoting Host Metabolism.

Some viruses, including human cytomegalovirus (HCMV), induce the synthesis of fatty acids and lipids to ensure that the lipid environment of infected cells supports virus replication. HCMV infection broadly reprograms metabolism to ensure central carbon metabolism provides the metabolites required for anabolic synthesis of nucleotides, proteins, and lipids while also meeting the energy demands placed on the infected cells. While HCMV infection increases the levels of most very long chain fatty acids (VLCFA), we found that the levels of erucic acid (EA), a C22:1 monounsaturated VLCFA, are reduced. Treating infected cells with EA disrupted a late step in virus replication, resulting in the release of virions with reduced infectivity. Moreover, we used lipidomics to determine that EA-treated cells had elevated levels of lipids containing a combination of a C22:1 tail and a VLC polyunsaturated fatty acid tail (VLC-PUFA). We demonstrate that fatty acid elongase 5 (ELOVL5) mediated production of VLC-PUFAs is stimulated by HCMV infection. ELOVL5 aided the increase in lipids with C22:1 plus VLC-PUFA tails following EA treatment and reduced the overall level of C22:1 in HCMV-infected cells. Moreover, we found that ELOVL5 mollified EA inhibition of HCMV replication, suggesting ELOVL5 plays a critical role in reducing the level of an endogenous FA with antiviral properties. Our study provides insight into how infection may increase the synthesis of an antiviral metabolite or FA and how the virus may evade their antiviral effect by promoting their metabolism.