A Conserved Natural Killer Cell Transcriptional Fingerprint in Rhesus Macaque Models of Acute Viral Infections

Natural killer (NK) cell activation and function are controlled by highly complex transcriptional programs. To leverage NK cells against human immunodeficiency virus and other diseases, a more complete understanding of signaling and metabolic dynamics is needed. In this study, we utilize a rhesus macaque (RM) model to define the transcriptomic profile of NK cells during acute lentiviral infection and to map the changes in this profile as infection progresses to the early chronic phase. Using a novel summary gene set for NK cell cytokine stimulation, we report synchronous metabolic and signaling transcriptional patterns that underlie established features of NK cell dysfunction. Assessing gene expression induced by the SARS-CoV-2 challenge allowed us to confirm a set of core conserved gene pathways central to RM NK cell activation across diverse acute viral contexts.