Fig. 1: Host nutrient metabolism is altered in response to viruses.

a, Viruses such as HCV and SARS-CoV-2 interact with entry/metabolic factors to increase fatty acid synthesis, triglycerides and lipid droplets essential for replication and trafficking of viruses to the cell membrane. b, Interactions between HIV and its entry/metabolic factors trigger PI3K–mTOR–HIF-1α activation, transcription of glycolytic genes, Glut1 trafficking to the cell membrane and increases in glucose uptake and glycolysis. Viruses such as SARS-CoV-2 may also activate PPAR-γ, driving its translocation to the nucleus and inducing lipogenic genes. c, Infection by viruses such as HIV, AdV, ZIKV and HCMV increase glutamine uptake and glutaminolysis. Glutaminolysis is the process by which glutamine is used to generate TCA cycle intermediates when pyruvate becomes limited. Glutamine is converted into glutamate by GLS, which is converted to α-ketoglutarate by GDH, restoring the TCA bioenergetic capacity. Increased TCA anaplerotic flux may also induce a ‘broken TCA cycle’ causing accumulation of inflammatory metabolites such as succinate, which can stabilize HIF-1α, succinylate glycolytic enzymes, increasing glycolysis and PPP, providing substrates for viral replication. AdV, adenovirus; CCR5, C-C chemokine receptor type 5; DGAT1, diacylglycerol O-acyltransferase 1; GDH, glutamate dehydrogenase; GLS, glutaminase; FA, fatty acid; αKG, alpha-ketoglutarate; PPAR-γ, peroxisome proliferator-activated receptor gamma; S6K, p70 ribosomal S6 kinase; TAG, triacylglycerol.