In contrast, resting CD4+ T cells are more resistant to HIV-1 infection, thanks to expression of innate immune defenses (SAMHD1-mediated impaired reverse transcription, IFI16-mediated viral nucleic acid sensing and signaling), leading to abortive infection and to cell death induced by pyroptosis (although this is not observed in vitro upon cell-free virus infection). Here, IFI16 is linked to viral infectious disease.