ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response.
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 identifie...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-04-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008457 |
| _version_ | 1818581984909197312 |
|---|---|
| author | Xuan Zhong Lu Feng Ru Zang Cao-Qi Lei Qing Yang Hong-Bing Shu |
| author_facet | Xuan Zhong Lu Feng Ru Zang Cao-Qi Lei Qing Yang Hong-Bing Shu |
| author_sort | Xuan Zhong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T07:42:11Z |
| format | Article |
| id | doaj.art-cb403c639c9046ddafdb4cde4c50156f |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T07:42:11Z |
| publishDate | 2020-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-cb403c639c9046ddafdb4cde4c50156f2022-12-21T22:39:03ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-04-01164e100845710.1371/journal.ppat.1008457ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response.Xuan ZhongLu FengRu ZangCao-Qi LeiQing YangHong-Bing ShuThe 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.https://doi.org/10.1371/journal.ppat.1008457 |
| spellingShingle | Xuan Zhong Lu Feng Ru Zang Cao-Qi Lei Qing Yang Hong-Bing Shu ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response. PLoS Pathogens |
| title | ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response. |
| title_full | ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response. |
| title_fullStr | ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response. |
| title_full_unstemmed | ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response. |
| title_short | ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response. |
| title_sort | zfyve1 negatively regulates mda5 but not rig i mediated innate antiviral response |
| url | https://doi.org/10.1371/journal.ppat.1008457 |
| work_keys_str_mv | AT xuanzhong zfyve1negativelyregulatesmda5butnotrigimediatedinnateantiviralresponse AT lufeng zfyve1negativelyregulatesmda5butnotrigimediatedinnateantiviralresponse AT ruzang zfyve1negativelyregulatesmda5butnotrigimediatedinnateantiviralresponse AT caoqilei zfyve1negativelyregulatesmda5butnotrigimediatedinnateantiviralresponse AT qingyang zfyve1negativelyregulatesmda5butnotrigimediatedinnateantiviralresponse AT hongbingshu zfyve1negativelyregulatesmda5butnotrigimediatedinnateantiviralresponse |