In 2016, Gray et al. generated primary IFI16-depleted mice and human fibroblasts by CRISPR-Cas9 and revealed that IFI16 was dispensable for IFN type I production in response to transfected DNA ligands, DNA virus infection, and lentivirus infection.49 Dramatically, two subsequent studies reclaimed the essential role of IFI16 in cytosolic DNA sensation and IFN induction using gene editing technology.50,51 The controversy about IFI16 may be involved in its cell-specific function and is pending further investigation. This evidence concerns the gene IFI16 and lentivirus infection.