The USP18 protein adopts the characteristic hand-like structure of ubiquitin-specific-proteases (USPs), which consists of a finger, palm and thumb domain.

[9] This process requires STAT2 to traffic USP18 to the receptor [10][11][12] These events terminate signaling and draw cells into a refractory state with diminished sensitivity to future stimulation.

[17] Macrophages and dendritic cells are usually the first point of contact with pathogens, including lentiviruses.

Host restriction factors, including SAMHD1, mediate the innate immune response against these viruses.

USP18 downregulates p21 protein expression, which correlates with upregulated intracellular dNTP levels and the antiviral inactive form of SAMHD1.

[23] Fortunately, this previously lethal condition was recently demonstrated to be curable with a Janus kinase inhibitor and intensive supportive care.