Figure 1

SAMHD1 restricts HIV-1 infection in resting CD4⁺T-cells by limiting viral reverse transcription. SAMHD1 is a dNTP triphosphohydrolase that converts intracellular dNTPs to deoxynucleosides (dN) and inorganic triphosphates (PPP), thereby limiting HIV-1 reverse transcription in resting CD4⁺ T-cells. Treatment of resting CD4⁺ T-cells with SIVsm/HIV-2 Vpx-containing VLPs or expression Vpx in resting CD4⁺ T-cells results in proteasomal degradation of SAMHD1 and leads to HIV-1 integration and early gene transcription. SAMHD1-mediated HIV-1 restriction in resting CD4⁺ T-cells might contribute to different aspects of viral immunopathogenesis, including CD4⁺ T-cell depletion and establishment of viral reservoirs and latency. Establishing HIV-1 latency in resting CD4⁺ T-cells requires chemokine-induced modifications in the actin cytoskeleton . Env, HIV-1 envelope protein.