Taking into account that in ISG15−/− macrophages the early events in the infection cycle of two completely different viruses, VACV or FLuV, were aborted, and that this was at the level of virus endocytosis, at least for VACV, we considered that other cellular entry processes inherent to macrophage function, such as phagocytosis, could be controlled by ISG15. This evidence concerns the gene ISG15 and infection.