| First Author | Zhong X | Year | 2020 |
| Journal | PLoS Pathog | Volume | 16 |
| Issue | 4 | Pages | e1008457 |
| PubMed ID | 32251420 | Mgi Jnum | J:292942 |
| Mgi Id | MGI:6451298 | Doi | 10.1371/journal.ppat.1008457 |
| Citation | Zhong X, et al. (2020) ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response. PLoS Pathog 16(4):e1008457 |
| abstractText | The retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), including RIG-I and melanoma differentiation-associated gene 5 (MDA5), sense cytoplasmic viral RNA and initiate innate antiviral responses. How RIG-I and MDA5 are differentially regulated remains enigmatic. In this study, we identified the guanylate-binding protein (GBP) and zinc-finger FYVE domain-containing protein ZFYVE1 as a negative regulator of MDA5- but not RIG-I-mediated innate antiviral responses. ZFYVE1-deficiency promoted MDA5- but not RIG-I-mediated transcription of downstream antiviral genes. Comparing to wild-type mice, Zfyve1-/- mice were significantly protected from lethality induced by encephalomyocarditis virus (EMCV) that is sensed by MDA5, whereas Zfyve1-/- and Zfyve1+/+ mice were comparable to death induced by vesicular stomatitis virus (VSV) that is sensed by RIG-I. Mechanistically, ZFYVE1 interacted with MDA5 but not RIG-I. ZFYVE1 bound to viral RNA and decreased the ligand binding and oligomerization of MDA5. These findings suggest that ZFYVE1 acts as a specific negative regulator of MDA5-mediated innate immune responses by inhibiting its ligand binding and oligomerization. |
