Budding of Enveloped Viruses: Interferon-Induced ISG15—Antivirus Mechanisms Targeting the Release Process

Figure 2

The mechanism of inhibition of budding late in the process mediated by ISG15 expression in cells. Step 1: The ESCRT-III protein, CHMP5, binds to LIP5 in the cytosol. In the presence of ISG15-specific E1, E2, and E3 ISG15 ligase complex, ISG15 is conjugated to CHMP5 and the binding to LIP5 is lost. Step 2: The CHMP5-ISG15 conjugate accumulates in the budding complex on the membrane. The interaction between VPS4 and its coactivator LIP5 is blocked preventing activation of the ATPase through formation of the VPS4/LIP5 double hexamer structure. Step 3: CHMP2A is ISGylated in the presence of ISG15-CHMP5. This results in the loss of its binding to LIP5 and weakens its direct interaction to VPS4. Step 4: CHMP6 is ISGylated in the presence of ISG15-CHMP5. This results in weakening of its binding to VPS4. Step 5: VPS4 is released into the cytosol and virus budding is arrested. (This figure was modified from Figure 7 in [83].)