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.
Highlights
Overview of Lipid MetabolismCellular metabolism encompasses numerous pathways that mediate the synthesis and degradation of energy-providing compounds and molecular building blocks
Similar to that observed for human gammaherpesviruses, we found that fatty acid synthesis supports murine herpesvirus 68 (MHV68) replication, as evidenced by decreased viral replication following treatment with an inhibitor of acetyl-CoA carboxylase [82]
human cytomegalovirus (HCMV) infection induces a marked increase in 26-carbon fatty acids which are incorporated into the viral membrane, and vaccinia virus (VACV) encodes numerous proteins whose palmitoylation is required for efficient replication
Summary
Cellular metabolism encompasses numerous pathways that mediate the synthesis and degradation of energy-providing compounds and molecular building blocks. Thanks to a number of landmark studies and the seemingly universal importance of the metabolism for diverse viruses, the topic of cellular metabolism is enjoying renewed appreciation amongst virologists. We will discuss the interplay between cellular lipid metabolism and DNA virus infection, with a particular focus on the synthetic pathways. Lipid metabolism comprises multiple cellular pathways that mediate the synthesis and breakdown of compounds such as fatty acids, sterols, and other molecules. Similar to other metabolic pathways, many of the main players have been elucidated; the regulatory complexity of lipid metabolism is still an active area of investigation
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