Chewing the Fat: The Conserved Ability of DNA Viruses to Hijack Cellular Lipid Metabolism

Abstract

Viruses manipulate numerous host factors and cellular pathways to facilitate the replication of viral genomes and the production of infectious progeny. One way in which viruses interact with cells is through the utilization and exploitation of the host lipid metabolism. While it is likely that most-if not all-viruses require lipids or intermediates of lipid synthesis to replicate, many viruses also actively induce lipid metabolic pathways to sustain a favorable replication environment. From the formation of membranous replication compartments, to the generation of ATP or protein modifications, viruses exhibit differing requirements for host lipids. Thus, while the exploitation of lipid metabolism is a common replication strategy, diverse viruses employ a plethora of mechanisms to co-opt these critical cellular pathways. Here, we review recent literature regarding the exploitation of host lipids and lipid metabolism specifically by DNA viruses. Importantly, furthering the understanding of the viral requirements for host lipids may offer new targets for antiviral therapeutics and provide opportunities to repurpose the numerous FDA-approved compounds targeting lipid metabolic pathways as antiviral agents.

Keywords: DNA virus; MHV68; cholesterol; fatty acids; herpesvirus; lipids.

Figure 1

Summary of the interplay between DNA virus infection and cellular lipid metabolism. This model illustrates a number of enzymes and intermediates involved in the synthesis of cholesterol (purple, right side), fatty acids (pink, left side), and related compounds. The precursor acetyl-CoA feeds both the mevalonate and fatty acid synthesis pathways. Virus interactions with these compounds are indicated by green arrows. Solid black arrows indicate the direct conversion of one molecule to the next, whereas dashed arrows indicate additional steps that, for the sake of simplicity, are not depicted. To conserve space, prenyl and palmitoyl moieties are depicted with only eight carbons. MHV68 (murine herpesvirus 68), HCMV (human cytomegalovirus), EBV (Epstein–Barr virus), KSHV (Kaposi’s sarcoma herpesvirus), VACV (vaccinia virus), HSV1 (herpes simplex virus-1), ACC (acetyl-CoA carboxylase), FAS (fatty acid synthase), PAT (palmitoyl acyl transferase), ACLY (ATP citrate lyase), LCFA (long chain fatty acids), VLCFA (very long chain fatty acids), FA (fatty acids), FFA (free fatty acids), FPP (farnesyl pyrophosphate), GGPP (geranylgeranyl pyrophosphate), FTase (farnesyl transferase), GGTase (geranylgeranyl transferase).