Stealing the Keys to the Kitchen: Viral Manipulation of the Host Cell Metabolic Network

Abstract

Host cells possess the metabolic assets required for viral infection. Recent studies indicate that control of the host's metabolic resources is a core host-pathogen interaction. Viruses have evolved mechanisms to usurp the host's metabolic resources, funneling them towards the production of virion components as well as the organization of specialized compartments for replication, maturation, and dissemination. Consequently, hosts have developed a variety of metabolic countermeasures to sense and resist these viral changes. The complex interplay between virus and host over metabolic control has only just begun to be deconvoluted. However, it is clear that virally induced metabolic reprogramming can substantially impact infectious outcomes, highlighting the promise of targeting these processes for antiviral therapeutic development.

Keywords: citric acid cycle; energy; fatty acid; glycolysis; immunity; infection; lipid; metabolism; virus.

Figure 1

Small–Molecule Metabolic Contributions to Viral Infection. Production of infectious virions requires energy and biomolecular building blocks derived from the host cell metabolic network (A). A diverse set of host metabolic activities drives the mass production of viral nucleic acids (red), structural proteins (black octagons), non-structural proteins and phospholipid envelopes (both in black circles), and glycosylated proteins (white circles). Additionally, organization of viral maturation compartments has increasingly been found to be dependent on lipid-modifying enzymes (B). Viral infection has also been found to induce specific metabolic activities to form specialized virion components that are important to infection (C). Lastly, the evidence supporting the importance of small-molecule metabolism for immune regulation is increasing, as are the findings that these processes are targeted by viral infection (D).

Figure 2

The Metabolism of Glucose and Glutamine and Support of Viral Infection. Glucose and glutamine catabolism provide energy and reducing equivalents [ATP, NADH, NADPH (shown in red)] as well as the molecular precursors to synthesize virion components (shown in blue). Abbreviation: TCA, tricarboxylic acid cycle.