PRF1 and HIV infectious disease: The possible mechanisms include the followings: 1) HIV virus induces activation and dysfunction of NK cells; 2) decreased levels of perforin and granzyme A in NK cells may account for impaired NK cytotoxicity [63]; 3) NK cells are activated in vivo in HIV disease (Figs 2 and 5), therefore they are desensitized to be re-stimulated and function as ADCC in vitro; 4) DC and NK cell cross-talk is dysregulated through IL-12/IL-15 during HIV infection [64, 65]; and 5) changes in NK cell subsets in untreated HIV disease may play a role in their function.