Metabolic regulation of NK cell antiviral functions during cytomegalovirus infection

Abstract

Natural killer (NK) cells quickly mount cytotoxic responses, produce cytokines, and proliferate in response to infected or transformed cells. Moreover, they can develop memory, with enhanced effector responses following activation, in some cases with antigen specificity. To optimally execute these functions, NK cells undergo metabolic reprogramming. Here, we discuss the interplay between metabolism and NK cell function in the context of viral infections. We review findings supporting metabolic regulation of NK cell effector functions, with a focus on NK cell antiviral infection in the context of cytomegalovirus in the mouse (MCMV) and human (HCMV).

Keywords: cytokines; cytomegalovirus infection; cytotoxicity; interferon gamma; memory; metabolism; natural killer cells; proliferation.

Figure 1.. Metabolic requirements for antiviral NK cell functions in vivo.

A summary of the interplay between metabolic pathways and antiviral functions based on in vivo studies with MCMV demonstrating the consequences of disruption of different metabolic pathways. MCMV infection leads to mitochondrial changes in Ly49H+ NK cells, initially decreasing mitochondrial cell membrane potential (ψ) at day 7 post-infection. Metabolic pathway disruptions primarily affect proliferation, with impacts on viral control, host survival, and generation of a pool of memory NK cells, as indicated by the down arrows. Glycolysis is required for antigen-specific killing, while mTOR is needed for degranulation and granzyme B production. Checkmarks signify intact function despite pathway disruption. Figure created with Biorender.com.