The authors have demonstrated that: (i) infection of iMphs with HIV-1 induces USP18; (ii) depletion of USP18 with CRISPR/Cas9 increases iMph reactivity to IFNI, the phosphorylation of STAT1 and STAT2, the expression of IFN-stimulated genes and ultimately results in a significant restriction of HIV replication in iMphs. The gene discussed is USP18; the disease is infection.