Natural killer cell effector functions in antiviral defense

Natural killer (NK) cells are innate lymphoid cells involved in the control of tumors and viral infections. They provide protection by producing cytokines and by directly lysing target cells. Both effector mechanisms have been identified to contribute to viral control, depending on the context of infection. Activation of NK cells depends on the integration of signals received by cytokine receptors and activation and inhibitory receptors recognizing ligands expressed by virus-infected cells. While the control of viral infections by NK cells is well established, the signals perceived by NK cells and how these signals integrate to mediate optimal viral control have been focus of ongoing research. Here, we discuss the current knowledge on NK cell activation and integration of signals that lead to interferon gamma production and cytotoxicity in viral infections. We review NK cell interactions with viruses, with particular focus on murine cytomegalovirus studies, which helped elucidate crucial aspects of antiviral NK cell immunity.