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. 2017 Nov 10;8:1541. doi: 10.3389/fimmu.2017.01541

Figure 2.

Figure 2

SAMHD1 negatively regulates the innate immune sensing of HIV-1 DNA. SAMHD1 blocks HIV-1 infection through intracellular dNTP depletion, thus preventing the accumulation of viral DNA accessible to sensing by IFI16 and cyclic GMP-AMP synthase (cGAS) and the activation of the type-I interferon (IFN-I) response. The dNTPase activity of SAMHD1 is structurally regulated. Consecutive binding of dGTP/GTP and any dNTP to two allosteric sites provokes formation of the catalytically active tetramer, which can be destabilized by phosphorylation, oxidation, or the binding of single-stranded nucleic acids (ssNAs). dN, deoxynucleosides; PPPs, triphosphate; two linked letters S indicate the disulfide bond.