Table 2.
Hijacking of cGAS/STING signaling by viruses.
| Virus Family | Virus | Viral Protein | Target | Proposed Mechanism | Reference |
|---|---|---|---|---|---|
| Herpesviridae | |||||
| HSV-1 | UL37 | cGAS | Deamidation of cGAS | (Zhang et al., 2018) | |
| HSV-1 | ? | cGAS | Degradation of β-arrestin 2 to inhibit the activation of cGAS | (Zhang et al., 2020) | |
| HSV-1 | ? | DNA-PK | PARylating cGAS to inhibit its DNA-binding ability | (Wang et al., 2022) | |
| HSV-1 | UL41 | cGAS | Degradation of cGAS | (Su and Zheng, 2017) | |
| γ-HSV/α-HSV | ORF52/VP22 | cGAS | Restriction of cGAS-DNA phase separation | (Xu et al., 2021) | |
| HSV-1 | ? | TRIM32 TRIM41 |
Inhibiting the activation of STING and TBK1 | (Yu et al., 2021) | |
| HSV-1 | ? | MYSM1 | MYSM1 interacts with STING and cleaves STING K63-linked ubiquitination | (Tian et al., 2020) | |
| HSV-1 | ? | TBK1 | Decreasing lncRNA-GM to increase S-glutathionylation of TBK1 |
(Wang et al., 2020) | |
| HSV-1 | ? | TBK1 | Promoting TBK1 s-nitrosation | (Liu et al., 2021) | |
| HSV-1 | VP24 | TBK1; IRF3 | Abrogating the interaction between TBK1 and IRF3 |
(Zhang et al., 2016) | |
| HSV-1 | US3 | IRF3 | Hyperphosphorylation of IRF3 at Ser175 to prevent IRF3 activation | (Wang et al., 2013) | |
| HSV-1 | US3 | IFN-β | Interacting with β-catenin; IFN-β↓ |
(You et al., 2020) | |
| HSV-1 | VP1-2 | STING | Cleaving the K63-linked polyubiquitination chain of STING | (Bodda et al., 2020) | |
| HSV-1 | VP16 | NF-κB; IRF3 and CBP |
Inhibiting NF-κB activation; Blocking IRF3 to recruit its coactivator CBP | (Xing et al., 2013) | |
| HSV-1 | UL24 | NF-κB | Inhibit the activation of NF-κB; IFN-β↓ |
(Xu et al., 2017) | |
| HSV-1 | UL36 | NF-κB | Deubiquitinate IκBα to restrict NF-κB activation; IFN-β↓ |
(Ye et al., 2017) | |
| HSV-1 | UL46 | STING; TBK1 |
STING protein↓; IFN-β and ISG56 mRNA↓ |
(Deschamps and Kalamvoki, 2017) | |
| HSV-2 | ICP27 | IRF3 | Inhibiting phosphorylation and nuclear translocation of IRF3 | (Guan et al., 2019) | |
| HSV-2 | US1 | IRF3 | Interacting with DNA binding domain of IRF-3 | (Zhang et al., 2015) | |
| HSV-2 | ICP22 | IFN-I Signaling | Degradation of STAT1, STAT2, IRF9 and ISGF3 | (Zhang et al., 2020) | |
| MDV | RLORF4 | p65 and p50 | Interfering with their nuclear translocation | (Liu et al., 2019) | |
| MDV | VP23 | TBK1 | Inhibiting the interaction between IRF7 and TBK1;Suppressing IRF7 activation | (Gao et al., 2019) | |
| KSHV | ORF33 | STING PPM1G |
Reducing STING phosphorylation | (Yu et al., 2020) | |
| KSHV | ORF48 | PPP6C | Reducing STING phosphorylation | (Ni et al., 2020) | |
| KSHV | ORF50 | USP7 | Degradation of IRF3 and IRF7 | (Yu and Hayward, 2010) | |
| KSHV | ORF52 | cGAS | Disrupting cGAS binding to DNA | (Wu et al., 2015) | |
| KSHV | LANA | cGAS | Interacting with cGAS to inhibit the phosphorylation of TBK1 and IRF3 | (Zhang et al., 2016) | |
| KSHV | LANA | NF-κB | Inhibiting the NF-κB activation | (Mariggio et al., 2017) | |
| KSHV | vIRF1 | STING | Reducing STING phosphorylation; Inhibiting STING binding to TBK1 |
(Ma et al., 2015) | |
| HCMV | pUL83 | cGAS | Inhibiting enzymatic activity of cGAS | (Biolatti et al., 2018) | |
| HCMV | UL31 | cGAS | Inhibiting DNA binding to cGAS | (Huang et al., 2018) | |
| HCMV | UL42 | cGAS/STING | Inhibiting DNA binding to cGAS and translocation of MITA | (Fu et al., 2019) | |
| HCMV | UL82 | STING | Interacting with STING to inhibit the translocation of STING | (Fu et al., 2017) | |
| HCMV | UL94 | STING | Disrupting the dimerization and translocation of STING | (Zou et al., 2020) | |
| EBV | ? | TRIM29 | Degradation of STING | (Xing et al., 2017) | |
| EBV | Zta | TBK1 and IRF3 | Inhibiting TBK1 and IRF3 activation | (Wong et al., 2017) | |
| PRV | UL13 | IRF3 | Phosphorylating IRF3 to attenuate the binding of IRF3 to the IFN-β promoter |
(Bo et al., 2020) | |
| PRV | gE | IRF3 CBP |
IFN-β↓; CBP protein degradation |
(Lu et al., 2021) | |
| Coronaviridae | |||||
| HCoV-NL63 | PLP2-TM | STING | Interacting with STING and disrupts STING dimers; Suppressing K63-linked polyubiquitination of STING |
(Sun et al., 2012) (Clementz et al., 2010) |
|
| MERS-CoV | M protein | TBK1 | Suppressing TBK1-dependent phosphorylation and activation of IRF3 | (Lui et al., 2016) | |
| MERS-CoV | ORF4b | TBK1 | Interacting with TBK1; IFN-β↓ |
(Yang et al., 2015) | |
| SARS-CoV | PLpro-TM | STING | Interacting with STING; Inhibiting K63-linked polyubiquitination of STING |
(Chen et al., 2014) | |
| SARS-CoV-2 | M protein | TBK1 | Interacting with TBK1 to degrade TBK1 | (Sui et al., 2021) | |
| SARS-CoV-2 | ORF9b | STING; TBK1 |
Impeding the phosphorylation and nuclear translocation of IRF3 | (Han et al., 2021) | |
| SARS-CoV-2 | ORF3a; 3CL |
STING | Impeding the nuclear translocation of IRF3; Inhibiting K63-linked ubiquitination of STING |
(Rui et al., 2021) | |
| SARS-CoV-2 | nsp12 | IRF3 | Preventing the nuclear translocation of IRF3 | (Wang et al., 2021) | |
| SARS-CoV-2 | NSP5 | IRF3 | Preventing the nuclear translocation of IRF3 | (Fung et al., 2021) | |
| PEDV | PLP2 | STING | Inhibiting K63-linked polyubiquitination of STING |
(Xing et al., 2013) | |
| PEDV | N protein | TBK1 | Inhibiting the interaction between TBK1 and IRF3 | (Ding et al., 2014) | |
| PEDV | nsp1 | CBP | CBP protein degradation | (Zhang et al., 2016) | |
| PEDV | nsp15 | TBK1 IRF3 |
Degrading the RNA levels of TBK1 and IRF3 | (Wu et al., 2020) | |
| PEDV | PLP1 | ? | Interacting with PCBP2; IFN-β↓ |
(Zhang et al., 2020) | |
| Poxviridae | |||||
| VACV | ? | caspase-3 | Activated caspase-3 to cleave cGAS and IRF3 |
(Ning et al., 2019) | |
| CPXV/ECTV | ? | STING | Inhibiting STING dimerization and phosphorylation | (Georgana et al., 2018) | |
| VACV | ? | TBK1 | Decreasing lncRNA-GM to increase S-glutathionylation of TBK1 |
(Wang et al., 2020) | |
| VACV | F17 | mTOR | mTOR Dysregulation; Suppressing ISG responses. | (Meade et al., 2019) | |
| Papillomaviridae | |||||
| HPV | E7 | STING | Interacting with STING | (Lau et al., 2015) | |
| HPV | E7 | IFI16 TRIM21 |
Degradation of IFI16 | (Song et al., 2020) | |
| Adenoviridae | |||||
| Adenovirus | E1A | STING | Interacting with STING | (Lau et al., 2015) | |
| Adenovirus | E1A | IFN-I Signaling | SuppressingSTAT1 activation | (Look et al., 1998) | |
| Hepadnaviridae | |||||
| HBV | Polymerase | STING | Inhibiting K63-linked ubiquitination of STING | (Liu et al., 2014) | |
| HBV | ? | IRF3 | IRF3↓IFN-β↓ | (Shravanthi et al., 2015) | |
| HBV | ? | PTEN | Inhibiting IRF-3 nuclear translocation | (Kim et al., 2021) | |
| Orthomyxoviridae | |||||
| Influenza A virus | NS1 | mtDNA | Inhibition of mtDNA release and binding to cGAS | (Moriyama et al., 2019) | |
| Flaviviridae | |||||
| DENV | NS2B | cGAS | Degradation of cGAS | (Aguirre et al., 2017) | |
| DTMUV | NS2A | STING; TBK1 |
Impairing STING-STING binding; Reducing TBK1 phosphorylation | (Zhang et al., 2020) | |
| DTMUV | NS2B3 | STING | Cleaving STING | (Wu et al., 2019) | |
| HCV | NS4B | STING | Blocking interaction between STING and STING | (Nitta et al., 2013) | |
| HCV | NS4B | STING | Suppressing STING Accumulation | (Yi et al., 2016) | |
| ZIKV | NS1 | cGAS | Inhibiting the proteasomal degradation of caspase-1 to cleave cGAS | (Zheng et al., 2018) | |
| ZIKV | NS2B3 | STING | Cleaving STING | (Ding et al., 2018) | |
| Paramyxoviridae | |||||
| SeV | ? | caspase-3 | Activated caspase-3 to cleave cGAS and IRF3 |
(Ning et al., 2019) | |
| SeV | ? | TBK1 | Decreasing lncRNA-GM to increase S-glutathionylation of TBK1 |
(Wang et al., 2020) | |
| SeV | ? | ASB8 | Promoting the interaction of ASB8 with TBK1 to degrade TBK1 | (Guo et al., 2020) | |
| SeV | ? | TBK1 | Promoting TBK1 s-nitrosation | (Liu et al., 2021) | |
| SeV | ? | IRF3 | Degradation of IRF3 | (Wang et al., 2015) | |
| SeV | ? | PSMD14 | Degradation of IRF3 | (Wu et al., 2021) | |
| SeV | ? | RBCK1 | Increased RBCK1 to degrade IRF3 | (Zhang et al., 2008) | |
| NiV | matrix protein | IFN-I signaling | Interacting with TRIM6 to suppress TRIM6-mediated IFN-I signaling | (Bharaj et al., 2016) | |
| Picornaviridae | |||||
| FMDV | Lpro | TBK1 | Cleaving TBK1 | (Visser et al., 2020) | |
| FMDV | Lpro | IRF3/7 | Decreasing the protein level of IFR3/7 | (Wang et al., 2010) | |
| FMDV | Lpro | IFN-I; ISG | Decreasing the protein level of IFN-I and ISG | (Medina et al., 2020) | |
| mengovirus | L proteins | IFN-I | Inhibiting IFN-I gene transcription | (Hato et al., 2010) | |
| FMDV | Lpro | p65 | Degradation of p65 | (De Los Santos et al., 2007) | |
| Retroviridae | |||||
| HIV-1 | capsid | cGAS | Disrupting cGAS binding to viral DNA | (Cingoz and Goff, 2019) | |
| HIV-2/SIV | Vpx | STING | Inhibiting STING activation; Interfering with the nuclear translocation of NF-κB |
(Su et al., 2019) | |
| HTLV-1 | Tax | STING | Inhibiting K63-linked ubiquitination of STING and interactions between STING and TBK1 | (Wang et al., 2017) | |
| HTLV-1 | Tax | TBK1 | Inhibiting IRF3 phosphorylation | (Yuen et al., 2016) | |
| SIV | ? | STING | Including expression of NLRX1 | (Barouch et al., 2016) | |
| Rhabdoviridae | |||||
| VSV | ? | β-arrestin 2 | Degradation of β-arrestin 2 to inhibit the activation of cGAS | (Zhang et al., 2020) | |
| VSV | ? | TRIM32 TRIM41 |
Inhibiting the activation of STING and TBK1 | (Yu et al., 2021) | |
| VSV | ? | Kisspeptin/GPR54 signaling | Dephosphorylating TBK1 | (Huang et al., 2018) | |
| VSV | ? | lncRNA-GM | Decreasing lncRNA-GM to increase S-glutathionylation of TBK1 |
(Wang et al., 2020) | |
| VSV | ? | TRIM26 | Degradation of IRF3 | (Wang et al., 2015) | |
| VSV | ? | caspase-3 | Activated caspase-3 to cleave IRF3 |
(Ning et al., 2019) | |
| Phenuiviridae | |||||
| HRTV | NSs | TBK1 | Blocking the interaction between TBK1 and IRF3 |
(Ning et al., 2017) | |
| HRTV | NSs and others | IFN-I signaling | Dampening both STAT2 and STAT1 activities | (Feng et al., 2019) | |
| Peribunyaviridae | |||||
| GTV | NSs | TBK1, STAT2 |
Sequesters TBK1and STAT2 into the viral IBs and FSs. |
(Min et al., 2020) | |
| Asfarviridae | |||||
| ASFV | ? | STING | Inhibiting the activation of STING; IFN-β↓ |
(García-Belmonte et al., 2019) | |
| ASFV | MGF360-11L | TBK1 IRF3 |
Inhibiting the phosphorylation of TBK1 and IRF3 | (Yang et al., 2022) | |
| Parvoviridae | |||||
| FPV | NS2 | TBK1 | Disrupting the Interaction between STING and TBK1 | (Kang et al., 2017) | |
| HBoV | NP1 | IRF-3 | Interacting with DNA binding domain of IRF-3 | (Zhang et al., 2012) | |
| Arteriviridae | PRRSV/LDV/SHFV | nsp1 | CBP | CBP protein degradation | (Han and Yoo, 2014) |
| Circoviridae | PCV2 | Cap and its binding protein gC1qR | cGAS | Catalyzing the K48-linked ubiquitination | (Wang et al., 2021) |