Metabolic host response and therapeutic approaches to influenza infection

Abstract

Based on available metabolomic studies, influenza infection affects a variety of cellular metabolic pathways to ensure an optimal environment for its replication and production of viral particles. Following infection, glucose uptake and aerobic glycolysis increase in infected cells continually, which results in higher glucose consumption. The pentose phosphate shunt, as another glucose-consuming pathway, is enhanced by influenza infection to help produce more nucleotides, especially ATP. Regarding lipid species, following infection, levels of triglycerides, phospholipids, and several lipid derivatives undergo perturbations, some of which are associated with inflammatory responses. Also, mitochondrial fatty acid βoxidation decreases significantly simultaneously with an increase in biosynthesis of fatty acids and membrane lipids. Moreover, essential amino acids are demonstrated to decline in infected tissues due to the production of large amounts of viral and cellular proteins. Immune responses against influenza infection, on the other hand, could significantly affect metabolic pathways. Mainly, interferon (IFN) production following viral infection affects cell function via alteration in amino acid synthesis, membrane composition, and lipid metabolism. Understanding metabolic alterations required for influenza virus replication has revealed novel therapeutic methods based on targeted inhibition of these cellular metabolic pathways.

Functional and tissue enrichment analyses suggest that SARS-CoV-2 infection affects host metabolism and catabolism mediated by interference on host proteins

“…Viruses usually disrupt the metabolism of nucleotide synthesis favoring the need for rapid viral genome replication [ 27 ]. Regulation of catabolism of nucleic acids and their metabolites can contribute to viral pathogenesis [ 28 ]. For instance, SARS-CoV-2 nsp8 appears to reduce the catabolism capacity of the host exosome complex against viral mRNAs [ 29 ].…”

“…For instance, depletion of protein stores influences many aspects of morbidity and mortality from infectious diseases [ 53 ]. To support the large amounts of viral replication, the influenza virus appears to obtain essential amino acids reducing their levels in infected tissues [ 28 ]. Similarly, in this context, HIV-1 also induces a deep effect in host protein metabolism to sustain the replication [ 54 ].…”

MicroRNAs and Mammarenaviruses: Modulating Cellular Metabolism

“…In a recent review, Keshavarz and colleagues, based on available metabolomic studies, argued that influenza virus infection can affect with cellular metabolic pathways either directly or indirectly via stimulation of immune system mediators [ 62 ]. Curiously, through enhancing the activity of the mTORC1 complex, the influenza virus strengthens numerous metabolic pathways, including glycolysis, glutaminolysis, pentose phosphate, and fatty acid synthesis, to provide more ATP and structural materials for viral replication [ 62 , 63 , 64 ]. Mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that plays a critical role in the control of cellular growth and metabolism [ 65 ].…”

Coronavirus infection: An immunologists' perspective

“…The changes involve modifications at the membrane levels. 70 IFN promotes the increase in cholesterol membrane content. The plasma membrane becomes more rigid, decreasing the possibility of viral infection.…”