Table 1.
Manipulations of ISG15 and their effects on virus infections in different models.
| Alteration of ISG15 | Virus/Pathogen | Model system | Effect | Ref. |
|---|---|---|---|---|
| overexpression of ISG15 | Pseudorabies Virus (PRV) | inducible cell line stably expressing the pISG15 gene | Inhibition of PRV replication reducing the viral titers and mRNA levels of PRV | [120] |
| Stable overexpression or knockdown of ISG15 | Classical Swine Fever Virus (CSFV) | Porcine Alveolar Macrophages (PAMs) | Loss of ISG15 led to abnormal proliferation of CSFV. Mechanism: the loss of ISG15 lead to loss of beclin-1 (BECN1) ISGylation that inhibits the autophagy process, which is necessary for CSFV replication | [121] |
| siRNA against ISG15 | Zika Virus (ZIKV) | Human Corneal Epithelial Cells (Pr. HCEC) | Silencing ISG15 results in increase ZIKV | [122] |
| ISG15 KO | SARS-CoV-2flaviviruses and picornaviruses | Mainly KO cell line: MEF / HeLa | ISGylation of MDA5 protein is crucial for sensing the viral nucleic acids recognition and triggers the immune response | [123] |
| ISG15 KO | Paramyxoviruses | A549-ISG15−/−cells | Rapid induction of ISGs synthesis | [124] |
| ISG15 KO | HIV | Human B cell precursor leukemia cell line, BlaER1 and THP-1 cells | Accumulation of misfolded dominant negative p53 resulting in enhance of HIV replication (functional p53 is required for p21 function: p21 acts as an inactivator of dNTP synthesis and activator of the restriction factor SAMHD1) |
[125] |
| ISG15 KO | Toxoplasma gondii | HeLa (cervical) and A549 (lung) cells. | ISG15 KO resulted in a decrease of the IFNγ response to the pathogen, impaired recruitment of the following adaptors: p62, NDP52, and LC3 to the parasitophorous vacuole. These effects prevent the restriction of the parasite growth | [126] |
| Cell lines expressing sub genomic replicons and replicon virus-like particles+ siRNA against ISG15+ O.E of ISG15/HERC | Flaviviruses | A549 cells | O.E of ISG15 (and HERC5) leads to reduced replication by suppressing the ALIX and CHMP4A pathway, two of the host’s proteins that are necessary for viral replication. The depletion of ISG15 results in enhancement of the effect observed in ALIX KO cell line. | [127] |
| ISG15 KO cells | Viral Hemorrhagic Septicemia Virus (VHSV) | EPC cells | Impaired viral replication, as compared to MX1 KO cell, even if the cells are pretreated with poly I:C | [128] |
A thorough summary of the impact of ISG15 on viral infection in human and mouse models was published by Lenchow D. in 2013 [78]. Here we expand the list with data published after 2013.