Blocking the SUMO cascade promoted infection in contexts where SAMHD1 was antivirally active (MDMs and differentiated THP1 cells infected by HIV-1 or HIV-2∆Vpx), but not when its function was suppressed by either T592 phosphorylation (dividing THP1 cells, HIV-1 infection) or Vpx-mediated degradation (VLP-Vpx treated MDMs, infection by HIV-1; differentiated THP1 cells, infection by HIV-2) (Fig. 6). The gene discussed is SAMHD1; the disease is HIV-1 infection.