ISG15 and HIV-1 infection: In addition, while early studies indicated ISG15 deficiency inhibits HIV-1 infection (Bosque and Planelles, 2009), subsequent mechanistic analyses revealed that this is due to free cellular ISG15 aids the stabilization of the ubiquitin-specific peptidase 18 (USP18), a negative regulator of type I interferon (IFN-I) signaling.