Viruses recognized by ZBP1
| Virus | Family | Proposed antiviral function(s) | Role(s) in in vivo mouse models | Viral ZBP1 antagonist | ZBP1 agonist | References |
|---|---|---|---|---|---|---|
| MCMV | Herpesviridae (large dsDNA) | Necroptosis | Restriction of viral replication Protective | M45 (vIRA) inhibits necroptosis | RNA | Jiao et al., 2020; Maelfait et al., 2017; Sridharan et al., 2017; Upton et al., 2012 |
| UV-inactivated human cytomegalovirus | Contribution to type I IFN response | n.a. | UL36 potentially inhibits necroptosis | n.d. | DeFilippis et al., 2010 | |
| HSV-1 | Necroptosis and apoptosis (and pyroptosis in BMDMs) Contribution to type I IFN response and inflammatory cytokine production Potential inhibition of ICP0-mediated degradation of IFI16 | Restriction of viral replication | ICP6 (UL39) inhibits necroptosis | n.d. | Furr et al., 2011; Guo et al., 2018; Jeffries et al., 2022; Lee et al., 2021; Pham et al., 2013; Takaoka et al., 2007 | |
| HSV-2 | Necroptosis? Contribution to type I IFN response | n.d. | ICP10 (UL39) potentially inhibits necroptosis | n.d. | Triantafilou et al., 2014 | |
| VZV | Apoptosis | n.d. | Triplex capsid subunit 1 (ORF20) inhibits caspase-dependent cell death | n.d. | Steain et al., 2020 | |
| Vaccinia virus | Poxviridae (large dsDNA) | Necroptosis | Restriction of viral replication Protective | E3 (E3L) sequesters Z-RNA | Z-RNA | Koehler et al., 2017, 2021 |
| IAV | Orthomyxoviridae (−ssRNA) | Apoptosis and necroptosis (and pyroptosis in BMDMs) Contribution to inflammatory cytokine production | Restriction of viral replication Protective or contribution to immunopathology | n.d. | Viral Z-RNA (e.g., subgenomic RNA) | Karki et al., 2022; Kuriakose et al., 2016; Momota et al., 2020; Thapa et al., 2016; Zhang et al., 2020 |
| SARS-CoV-2 | Coronaviridae (+ssRNA) | Apoptosis and necroptosis (and pyroptosis in BMDMs) Contribution to inflammatory cytokine production | No effect on viral replication Causes immunopathology | n.d. | Viral Z-RNA | Li et al., 2023; Peng et al., 2022 |
| MHV | Apoptosis and necroptosis (and pyroptosis in BMDMs) | Causes immunopathology following IFN-β treatment | n.d. | n.d. | Karki et al., 2022 | |
| Zika virus | Flaviviridae (+ssRNA) | IRF1-dependent upregulation of IRG1 resulting in a metabolic antiviral state in neurons | Restriction of viral replication, better survival | n.d. | n.d. | Daniels et al., 2019; Rothan et al., 2019 |
| West Nile virus | Flaviviridae (+ssRNA) | n.d. | Restriction of viral replication, better survival | n.d. | n.d. | Rothan et al., 2019 |
| Virus | Family | Proposed antiviral function(s) | Role(s) in in vivo mouse models | Viral ZBP1 antagonist | ZBP1 agonist | References |
|---|---|---|---|---|---|---|
| MCMV | Herpesviridae (large dsDNA) | Necroptosis | Restriction of viral replication | M45 (vIRA) inhibits necroptosis | RNA | |
| UV-inactivated human cytomegalovirus | Contribution to type I IFN response | n.a. | UL36 potentially inhibits necroptosis | n.d. | ||
| HSV-1 | Necroptosis and apoptosis (and pyroptosis in BMDMs) | Restriction of viral replication | ICP6 (UL39) inhibits necroptosis | n.d. | ||
| HSV-2 | Necroptosis? | n.d. | ICP10 (UL39) potentially inhibits necroptosis | n.d. | ||
| VZV | Apoptosis | n.d. | Triplex capsid subunit 1 (ORF20) inhibits caspase-dependent cell death | n.d. | ||
| Vaccinia virus | Poxviridae (large dsDNA) | Necroptosis | Restriction of viral replication | E3 (E3L) sequesters Z-RNA | Z-RNA | |
| IAV | Orthomyxoviridae (−ssRNA) | Apoptosis and necroptosis (and pyroptosis in BMDMs) | Restriction of viral replication | n.d. | Viral Z-RNA (e.g., subgenomic RNA) | |
| SARS-CoV-2 | Coronaviridae (+ssRNA) | Apoptosis and necroptosis (and pyroptosis in BMDMs) | No effect on viral replication | n.d. | Viral Z-RNA | |
| MHV | Apoptosis and necroptosis (and pyroptosis in BMDMs) | Causes immunopathology following IFN-β treatment | n.d. | n.d. | ||
| Zika virus | Flaviviridae (+ssRNA) | IRF1-dependent upregulation of IRG1 resulting in a metabolic antiviral state in neurons | Restriction of viral replication, better survival | n.d. | n.d. | |
| West Nile virus | Flaviviridae (+ssRNA) | n.d. | Restriction of viral replication, better survival | n.d. | n.d. |
Viruses known to be detected by ZBP1 are shown, along with viral families and proposed antiviral functions of ZBP1. Where these have been determined, in vivo roles of ZBP1, viral ZBP1 antagonists, and nucleic acid agonists of ZBP1 are given. n.d., not determined; n.a., not applicable.
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