| First Author | Hasan M | Year | 2013 |
| Journal | Nat Immunol | Volume | 14 |
| Issue | 1 | Pages | 61-71 |
| PubMed ID | 23160154 | Mgi Jnum | J:191073 |
| Mgi Id | MGI:5460923 | Doi | 10.1038/ni.2475 |
| Citation | Hasan M, et al. (2013) Trex1 regulates lysosomal biogenesis and interferon-independent activation of antiviral genes. Nat Immunol 14(1):61-71 |
| abstractText | The sensing of viral nucleic acids by the innate immune system triggers the production of type I interferons, which activates interferon-stimulated genes (ISGs) and directs a multifaceted antiviral response. ISGs can also be activated through interferon-independent pathways, although the precise mechanisms remain elusive. Here we found that the cytosolic exonuclease Trex1 regulated the activation of a subset of ISGs independently of interferon. Both Trex1(-/-) mouse cells and Trex1-mutant human cells had high expression of genes encoding antiviral molecules ('antiviral genes') and were refractory to viral infection. The interferon-independent activation of antiviral genes in Trex1(-/-) cells required the adaptor STING, the kinase TBK1 and the transcription factors IRF3 and IRF7. We also found that Trex1-deficient cells had an expanded lysosomal compartment, altered subcellular localization of the transcription factor TFEB and diminished activity of the regulator mTORC1. Together our data identify Trex1 as a regulator of lysosomal biogenesis and interferon-independent activation of antiviral genes and show that dysregulation of lysosomes can elicit innate immune responses. |
