Other
18 Authors
- Wang Y,
- Droit L,
- Hill R,
- Deng H,
- Yang X,
- Kalugotla G,
- Lu Q,
- Li Y,
- Wu C,
- Baldridge MT,
- Ingle H,
- Lee S,
- Borella NR,
- Lawrence D,
- Desai C,
- Zhang J,
- Rodgers R,
- Peterson ST
| First Author | Lee S | Year | 2022 |
| Journal | Autophagy | Volume | 18 |
| Issue | 5 | Pages | 1062-1077 |
| PubMed ID | 34520306 | Mgi Jnum | J:325742 |
| Mgi Id | MGI:7287363 | Doi | 10.1080/15548627.2021.1968607 |
| Citation | Lee S, et al. (2022) Intestinal antiviral signaling is controlled by autophagy gene Epg5 independent of the microbiota. Autophagy 18(5):1062-1077 |
| abstractText | Mutations in the macroautophagy/autophagy gene EPG5 are responsible for Vici syndrome, a human genetic disease characterized by combined immunodeficiency. Previously, we found that epg5(-/-) mice exhibit hyperinflammation in the lungs mediated by IL1B/IL-1beta and TNF/TNFalpha, resulting in resistance to influenza. Here, we find that disruption of Epg5 results in protection against multiple enteric viruses including norovirus and rotavirus. Gene expression analysis reveals IFNL/IFN-lambda responsive genes as a key alteration. Further, mice lacking Epg5 exhibit substantial alterations of the intestinal microbiota. Surprisingly, germ-free mouse studies indicate Epg5-associated inflammation of both the intestine and lung is microbiota-independent. Genetic studies support IFNL signaling as the primary mediator of resistance to enteric viruses, but not of microbial dysbiosis, in epg5(-/-) mice. This study unveils an important role, unexpectedly independent of the microbiota, for autophagy gene Epg5 in host organism protection by modulating intestinal IFNL responses.Abbreviations: CTNNB1: catenin (cadherin associated protein), beta 1; DAPI: 4',6-diamidino-2-phenylindole; EPG5: ectopic P-granules autophagy protein 5 homolog (C. elegans); FT: fecal transplant; IFI44: interferon-induced protein 44; IFIT1: interferon-induced protein with tetratricopeptide repeats 1; IFNG/IFN-gamma: interferon gamma; IFNL/IFN-lambda: interferon lambda; IFNLR1: interferon lambda receptor 1; IL1B/IL-1beta: interleukin 1 beta; ISG: interferon stimulated gene; GF: germ-free; LEfSe: linear discriminant analysis effect size; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MNoV: murine norovirus; MX2: MX dynamin-like GTPase 2; OAS1A: 2'-5' oligoadenylate synthetase 1A; RV: rotavirus; SPF: specific-pathogen free; SQSTM1/p62: sequestosome 1; STAT1: signal transducer and activator of transcription 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK-binding kinase 1; TNF/TNFalpha: tumor necrosis factor. |
