Fig. 7: Contribution of nucleic acid binding to the antiviral activity of SAMHD1.

Oligonucleotide-dependent oligomerization of SAMHD1 may function as a distinct dNTPase activation mechanism that is critical for restriction of retroviral replication but not for the overall depletion of cellular dNTP content. Alternatively, it may contribute to retroviral restriction in a dNTPase-independent fashion by stalling reverse transcription, recruiting other factors, or promoting degradation of viral nucleic acids. The GpsN modification (black star) may be involved in human innate immunity or may simply mimic some other structural feature present in the physiological nucleic acid ligands of SAMHD1.