ISG15 Is Counteracted by Vaccinia Virus E3 Protein and Controls the Proinflammatory Response against Viral Infection

Conjugation of ISG15 inhibits replication of several viruses. Here, using an expression system for assaying human and mouse ISG15 conjugations (ISGylations), we have demonstrated that vaccinia virus E3 protein binds and antagonizes human and mouse ISG15 modification. To study ISGylation importance in poxvirus infection, we used a mouse model that expresses deconjugating proteases. Our results indicate that ISGylation restricts in vitro replication of the vaccinia virus VV E3L mutant but unconjugated ISG15 is crucial to counteract the inflammatory response produced after VV E3L infection
This work was supported by grants from the Spanish Ministry of Health, FIS2011-00127, and UAM-Banco de Santander to S.G. and was also partly supported by NIAID grant U19AI083025 to A.G.-S