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. 2021 Nov 25;9:788410. doi: 10.3389/fcell.2021.788410

TABLE1.

Interaction between ISG15 and viral proteins.

Viral proteins Biological effects after ISGylation Impact on viral infection Reference
IVA NS1 ISG15 inhibits viral proteins nuclear translocation and restores host antiviral responses Inhibits IBV replication (Tang et al., 2010; Zhao et al., 2010)
IBV NPs ISGylation of NPs inhibit the oligomerization of unmodified NPs, which impedes viral RNA synthesis Inhibits IBV replication Zhao et al. (2016)
CVB3 2Apro ISG15 inhibits its protease activity to restore host protein translation Inhibits CVB3 replication Rahnefeld et al. (2014)
HIV Gag ISG15 inhibits the monoubiquitination of Gag protein and block its interaction with TSG101 Inhibits the emergence and release of HIV. Okumura et al. (2006)
EBOV VP40 ISGylation of NEDD4 ubiquitin-binding enzyme inhibits its interaction with VP40 Inhibits the budding and release of Ebola virus (Yasuda et al., 2003; Okumura et al., 2008)
ASLV Gag The ISGylation of CHMP5 limits the membrane recruitment of Vps4 and its interaction with the ASLV Gag Inhibits the ASLV budding complex, then inhibits the release of intracellular virus-like particles Pincetic et al. (2010)
SARS PLpro MERS PLpro PLpro protease is a virus-encoded DUB, which active on ubiquitin like molecule ISG15 Negatively regulates the innate immune response to the virus Rut et al. (2020)