In addition, our results showed that SAMHD1 is able to reduce MAPK p38 phosphorylation, providing further evidence of a broader role for SAMHD1 in modulating several signaling cascades that could affect cellular transcription, inflammation, and innate immune activation in response to HIV-1 infection and proinflammatory stimuli (Fig. 7). Here, SAMHD1 is linked to HIV-1 infection.