NK cells against viral infection: from basic biology to immunotherapy

Abstract Natural killer (NK) cells, a pivotal component of the innate immune system, exert indispensable roles in antiviral immunity by directly eliminating virus-infected cells and modulating adaptive immune responses. This review systematically synthesizes the biological characteristics of NK cells and their multifaceted functions against viral infections. The bidirectional crosstalk between NK cells and viruses is elucidated, with a focus on NK cell adaptive features and viral evasion strategies during specific viral infections. Furthermore, potential therapeutic targets and cutting-edge immunotherapeutic strategies due to modulation of NK cell activities are summarized, including monoclonal antibodies (mAbs), chimeric antigen receptor (CAR)-modified NK cells, and adjuvant therapy with Chinese herbal medicines (CHMs). Recent clinical evidence and preclinical advances are integrated to provide a comprehensive framework for understanding NK cell-mediated antiviral immunity, identifying novel insights to guide the development of precise, effective immunotherapies for combating refractory viral infections.