The NAD cap is removed in human cells by theseenzymes: Nudt12,35 Nudt16,36 and DXO.13 Nudt12 and Nudt16members of the NudiX family,cleave the pyrophosphate backbone of free NAD37 and NAD–RNA, and, thus, reduce the intracellular concentrationsof free NAD and NAD–RNA, whereas DXO cleaves the entire moietyof NAD from RNA and does not affect the intracellular concentrationof free NAD (Figure 3A).13 To investigate solely the role ofNAD–RNA (not free NAD) in HIV-1 infection, we focused on theDXO decapping enzyme. Here, DXO is linked to HIV-1 infection.