Indeed, the early targets of infection by HIV are almost exclusively CD4+ T cells, with minimal infection of myeloid cells.90,91 Still, we did see variability in SAMHD1 among myeloid cells, in that expression levels were lower in those from the spleen and LN relative to other tissues; this may explain the enhanced susceptibility of LN myeloid cells to HIV infection.92 Further supporting the notion of SAMHD1 playing a key role in broad restriction of HIV infection of myeloid cells is our finding that HIV-fused myeloid cells express high levels of SAMHD1 relative to their unfused counterparts. Here, CD4 is linked to HIV infectious disease.