Interplay between Cellular Metabolism and Cytokine Responses during Viral Infection

Abstract

Metabolism and immune responses are two fundamental biological processes that serve to protect hosts from viral infection. As obligate intracellular pathogens, viruses have evolved diverse strategies to activate metabolism, while inactivating immune responses to achieve maximal reproduction or persistence within their hosts. The two-way virus-host interaction with metabolism and immune responses choreograph cytokine production via reprogramming metabolism of infected cells/hosts. In return, cytokines can affect the metabolism of virus-infected and bystander cells to impede viral replication processes. This review aims to summarize our current understanding of the cross-talk between metabolic reprogramming and cytokine responses, and to highlight future potential research topics. Although the focus is placed on viral pathogens, relevant findings from other microbes are integrated to provide an overall picture, particularly when corresponding information on viral infection is lacking.

Innate Immune Evasion by Human Respiratory RNA Viruses

“…Besides these different responses, most of which are IFN-mediated, small non-coding (micro, circular, ...) RNAs, RNAi, and IFN-independent antiviral responses can be regarded as part of the innate immune response package as well [29][30][31]. An emerging hot topic is also the interplay of innate immune response with cellular metabolism, so-called immunometabolism, which likely is quite relevant for respiratory viral infections [4,32,33]. The general idea is that immune cells such as macrophages and DCs adapt the choice for the use of their metabolic systems to an immune-activated situation that requires increased amounts of energy.…”

“…To facilitate comparison between the respiratory viruses described here, known and arguably important innate immune evasion strategies are listed, and for each strategy it is discussed how each virus group exploits its own mechanism. Innate immune evasion obviously links to the innate immune responses that are known to be elicited by respiratory and other (RNA) viruses, and while this will be elaborated to a limited extent below, they have also been reviewed comprehensively in recent reviews by others [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17].…”

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19

“…JAK-1 and JAK-2 (JAK 1/2) kinase are found in the cell cytoplasm and are associated with key cytokine receptors and activating kinases. Upon activation, JAK 1/2 induce downstream activation of signal transducer and activator of transcription (STAT) protein, with transduction of the signal and the final transcription of several genes involved in immune cells proliferation, differentiation, activation/inhibition, and survival/ apoptosis [283].…”

“…Generally, IFN-α/β would be considerably upregulated by viral infections: studies found that distinct anti-viral activities correlate with virus-specific expression levels of Interferon-stimulated genes (ISGs) subsets. For instance, some ISGs have strong anti-viral effects while others promote viral replication in vitro [283]. Macrophages produce significant levels of IFN-α/β, IL-1β, TNF-α, chemokines, and IL-18 [284].…”

Fueling influenza and the immune response: Implications for metabolic reprogramming during influenza infection and immunometabolism

“…Glutamine is a vital carbon source during productive viral infections. 9,135 Conversely, glutamine boosts the inflammatory response. For example, extra glutamine increased IFN-inducible genes in T cells, thereby inhibiting herpes reactivation, 136 and increased activated intraepithelial lymphocyte IL-2 and IFN-γ production.…”