| First Author | Cheng WY | Year | 2018 |
| Journal | Front Immunol | Volume | 9 |
| Pages | 1297 | PubMed ID | 29963044 |
| Mgi Jnum | J:265099 | Mgi Id | MGI:6199031 |
| Doi | 10.3389/fimmu.2018.01297 | Citation | Cheng WY, et al. (2018) The cGas-Sting Signaling Pathway Is Required for the Innate Immune Response Against Ectromelia Virus. Front Immunol 9:1297 |
| abstractText | Activation of the DNA-dependent innate immune pathway plays a pivotal role in the host defense against poxvirus. Cyclic GMP-AMP synthase (cGAS) is a key cytosolic DNA sensor that produces the cyclic dinucleotide cGMP-AMP (cGAMP) upon activation, which triggers stimulator of interferon genes (STING), leading to type I Interferons (IFNs) production and an antiviral response. Ectromelia virus (ECTV) has emerged as a valuable model for investigating the host-Orthopoxvirus relationship. However, the role of cGas-Sting pathway in response to ECTV is not clearly understood. Here, we showed that murine cells (L929 and RAW264.7) mount type I IFN responses to ECTV that are dependent upon cGas, Sting, TANK binding kinase 1 (Tbk1), and interferon regulatory factor 3 (Irf3) signaling. Disruption of cGas or Sting expression in mouse macrophages blocked the type I IFN production and facilitated ECTV replication. Consistently, mice deficient in cGas or Sting exhibited lower type I IFN levels and higher viral loads, and are more susceptible to mousepox. Collectively, our study indicates that the cGas-Sting pathway is critical for sensing of ECTV infection, inducing the type I IFN production, and controlling ECTV replication. |
