Viral Manipulation of Host Cell Metabolism

Viruses routinely rewire metabolic circuits within their host cells to secure the resources necessary for replication and assembly. Upon infection, viruses manipulate pathways of energy production and macromolecular synthesis to create a bioenergetic and biosynthetic environment tailored to their lifecycle. Key targets include glycolysis, the tricarboxylic acid cycle, nucleotide and lipid synthesis, and amino acid utilisation. Some viruses activate oncogenic transcription factors to enhance nutrient uptake, while others repurpose stress‐response kinases to maintain metabolic flux. These alterations not only fuel viral progeny production but can also modulate immune signalling, for instance by shifting metabolite levels that impair antiviral defences. Analytic advances in metabolomics and flux analysis have revealed virus‐specific metabolic programmes, ranging from increased glycolytic throughput in norovirus infection to glutamine dependence in oncogenic herpesvirus latency. An improved understanding of these processes is of global importance, offering potential for broad‐spectrum antivirals that target conserved metabolic nodes rather than virus‐specific proteins. Moreover, elucidation of host‐pathogen metabolic interactions may inform therapeutic strategies against virus‐induced pathologies such as cancer.

Research from Nature Portfolio

Studies have demonstrated that hepatitis B virus co-opts host glycolysis to evade innate immune sensors by promoting lactate production, which binds to mitochondrial antiviral-signalling protein (MAVS) and prevents its activation. Pharmacological or genetic disruption of key glycolytic enzymes restored antiviral signalling and reduced viral replication in vitro and in animal models. In a separate investigation, adenovirus infection was found to initiate MYC-driven upregulation of glutamine transporters and catabolic enzymes, enhancing glutaminolysis to support nucleotide biosynthesis and energy production. Inhibition of glutaminase markedly diminished adenoviral, herpes simplex and influenza A replication in primary cells, highlighting a conserved metabolic vulnerability exploitable for antiviral therapy.

Viral Manipulation of Host Cell Metabolism publication trend

The graph below shows the total number of articles in viral manipulation of host cell metabolism across all publications each year (not limited to Nature Index journals).

Technical terms

Glycolysis: A cytosolic pathway converting glucose to pyruvate with concomitant ATP production.

Tricarboxylic acid cycle: A mitochondrial sequence of reactions that oxidises acetyl-CoA to generate reducing equivalents and biosynthetic precursors.

Glutaminolysis: The metabolic conversion of glutamine to α-ketoglutarate to fuel the TCA cycle and provide nitrogen for nucleotide synthesis.

Anaplerosis: Pathways that replenish TCA cycle intermediates consumed for biosynthesis.

MAVS: Mitochondrial antiviral-signalling protein that orchestrates innate immune responses to viral RNA.

References

1. Viral hijacking of cellular metabolism. BMC Biology (2019).
2. Hepatitis B virus rigs the cellular metabolome to avoid innate immune recognition. Nature Communications (2021).
3. MYC-induced reprogramming of glutamine catabolism supports optimal virus replication. Nature Communications (2015).
4. Latent KSHV Infected Endothelial Cells Are Glutamine Addicted and Require Glutaminolysis for Survival. PLOS Pathogens (2015).
5. Hijacking the Supplies: Metabolism as a Novel Facet of Virus-Host Interaction. Frontiers in Immunology (2019).
6. Glycolysis Is an Intrinsic Factor for Optimal Replication of a Norovirus. mBio (2019).