Single-cell sequencing reveals NK cell dysregulation during chronic HIV infection and identifies transitional NK cell cytotoxicity related to HIV reservoir decay

BACKGROUND: Natural killer (NK) cells, as an integral component of the innate immune system, assume a pivotal role in combating viral infections. Our understanding of how human immunodeficiency virus (HIV) infection affects NK cell heterogeneity remains limited. METHODS: T cells. FINDINGS: NK-MKI67, increased following HIV infection, enriched in S and G2/M phases cells, respectively, with distinct metabolic profiles. Notably, the cytotoxicity score of the c5-Transitional NK subset before ART was associated with HIV-DNA decline over time. INTERPRETATION: Our findings offer a comprehensive understanding of the cellular and molecular heterogeneity of NK cell immune response during HIV infection and offer insights for NK cell-based immunotherapies. FUNDING: Supported by grants from the National Natural Science Foundation of China (No. 82371766, 82572006, 82101837, and 82271857).