Hijacking the Supplies: Metabolism as a Novel Facet of Virus-Host Interaction

Abstract

Viral replication is a process that involves an extremely high turnover of cellular molecules. Since viruses depend on the host cell to obtain the macromolecules needed for their proper replication, they have evolved numerous strategies to shape cellular metabolism and the biosynthesis machinery of the host according to their specific needs. Technologies for the rigorous analysis of metabolic alterations in cells have recently become widely available and have greatly expanded our knowledge of these crucial host-pathogen interactions. We have learned that most viruses enhance specific anabolic pathways and are highly dependent on these alterations. Since uninfected cells are far more plastic in their metabolism, targeting of the virus-induced metabolic alterations is a promising strategy for specific antiviral therapy and has gained great interest recently. In this review, we summarize the current advances in our understanding of metabolic adaptations during viral infections, with a particular focus on the utilization of this information for therapeutic application.

Keywords: host-pathogen interaction; metabolism; metabolome; rhinovirus; virus.

Figure 1

Schematic overview of metabolic targets of DNA viruses. Different DNA viruses activate specific anabolic metabolic programs in host cells to ultimately support viral replication and virion maturation. Dashed arrows indicate a virus-mediated activation of the respective metabolic pathway or an activation of the transcription factor, respectively. HCMV, human cytomegalovirus; HSV-1, herpes simplex virus-1; KSHV, Kaposi's sarcoma-associated herpesvirus; VACV, vaccinia virus; GLUT, glucose transporter; ChREBP, carbohydrate-response element-binding protein; SREBP, sterol regulatory element-binding protein; α-KG, α-ketoglutarate; TCA, tricarboxylic acid cycle.

Figure 2

Post-transcriptional manipulation of the host cell metabolism by the RNA virus rhinovirus. Rhinovirus (RV) orchestrates an anabolic reprogramming of the host cell metabolism: RV induces PI3K-dependent trafficking of GLUT1-containing vesicles to the cell membrane, ultimately leading to increased glucose uptake. Subsequently, RV increases both glycolysis and glycogenolysis, providing TCA intermediates needed for anabolic lipogenesis. Additionally, RV infection activates the pentose phosphate pathway, resulting in elevated nucleotide levels that support viral replication. GLUT, glucose transporter; PI3K, phosphatidylinositol 3-kinase; RV, rhinovirus; TCA, tricarboxylic acid cycle.