Natural Killer (NK) cells are key players in the early control of viral infections and cancer. Historically considered as part of the innate immune system, NK cells are now recognized for their phenotypic and functional diversity, especially within tissues. Recent findings demonstrate their ability to acquire adaptive, antigen-specific features following viral infections, particularly in chronic settings such as human and murine cytomegalovirus (HCMV, MCMV). Despite these advances, the molecular mechanisms driving NK cell differentiation, adaptation, and tissue residency during viral infections remain largely unknown, especially in humans due to limited access to infected tissues, notably during the acute phase.
Non-human primates (NHP) represent the most relevant translational model to address these gaps, given their close immunological resemblance to humans and the possibility to conduct longitudinal, tissue-specific studies. Preliminary work from our team has demonstrated the presence of tissue-resident, adaptive-like NK cells in the lungs during SARS-CoV-2 infection and in secondary lymphoid tissues (SLT) during chronic SIV infection. Moreover, our data suggest a link between terminal NK cell differentiation and the acquisition of adaptive features, but the transcriptional programs governing these processes, particularly in the early phase of infection, remain undefined.
To overcome this, we will use high-resolution single-cell RNA sequencing (scRNA-seq) to dissect NK cell heterogeneity, differentiation pathways, and early tissue-specific adaptations during the acute phase of SARS-CoV-2 and SIV infections. Access to the single-cell platform is essential to define these mechanisms, providing new insights into NK cell-mediated immunity and potential antiviral interventions.
