Inhibition of host ISG15 by virus

The ISG15 protein is a ubiquitin-like modifier induced by interferon, which induces modification and somehow inhibits cellular and viral proteins . Like ubiquitin , ISG15 is conjugated to lysines on numerous target proteins through its conserved C-terminal region. This reaction is mediated by specific E1-activating, E2-conjugating, and E3-ligase enzymes, all of which are also IFN-inducible.

INFRA1 INFRA2 JAK1 TYK2 STAT2 STAT1 STAT1 STAT1 STAT1 STAT2 STAT2 sars E3 STAT1 STAT2 IRF9 IRF9 IRF9 NS1 ISG15

Viruses escape from the antiviral activity of ISG15 by using different mechanisms. The influenza B virus NS1 protein for instance blocks the covalent linkage of ISG15 to its target proteins by directly interacting with ISG15. The papain-like protease from the severe acute respiratory syndrome coronavirus cleaves ISG15 derivatives.This resluts in inactivation of host antiviral protein MDA-5.