ISG15 and infection: It was also observed that HERC5 and ISG15 are upregulated in response to infection caused by the Zika virus [116,117,118,119], Ebola virus [120,121,122,123], vaccinia virus [107], Kaposi’s sarcoma-associated herpesvirus (KSHV) [101], influenza B virus [124] and others (please see Table 1); however, the specific structural and biochemical modes of inhibition enacted by HERC5 and ISG15 in response to these pathogens is not fully understood.