Article ; Online: The aldehyde dehydrogenase ALDH1B1 exerts antiviral effects through the aggregation of the adaptor MAVS.
2024 Volume 17, Issue 818, Page(s) eadf8016
Abstract: Type I interferons (IFNs) are produced by almost all cell types and play a vital role in host defense against viral infection. Infection with an RNA virus activates receptors such as RIG-I, resulting in the recruitment of the adaptor protein MAVS to the ... ...
Abstract | Type I interferons (IFNs) are produced by almost all cell types and play a vital role in host defense against viral infection. Infection with an RNA virus activates receptors such as RIG-I, resulting in the recruitment of the adaptor protein MAVS to the RIG-I-like receptor (RLR) signalosome and the formation of prion-like functional aggregates of MAVS, which leads to IFN-β production. Here, we identified the aldehyde dehydrogenase 1B1 (ALDH1B1) as a previously uncharacterized IFN-stimulated gene (ISG) product with critical roles in the antiviral response. Knockout of ALDH1B1 increased, whereas overexpression of ALDH1B1 restricted, the replication of RNA viruses, such as vesicular stomatitis virus (VSV), Zika virus (ZIKV), dengue virus (DENV), and influenza A virus (IAV). We found that ALDH1B1 localized to mitochondria, where it interacted with the transmembrane domain of MAVS to promote MAVS aggregation. ALDH1B1 was recruited to MAVS aggregates. In addition, ALDH1B1 also enhanced the interaction between activated RIG-I and MAVS, thus increasing IFN-β production and the antiviral response. Furthermore, |
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MeSH term(s) | Animals ; Mice ; Aldehyde Dehydrogenase ; Antiviral Agents ; DEAD Box Protein 58 ; Influenza A virus ; Mice, Knockout ; Zika Virus ; Zika Virus Infection |
Chemical Substances | Aldehyde Dehydrogenase (EC 1.2.1.3) ; Antiviral Agents ; DEAD Box Protein 58 (EC 3.6.4.13) ; IPS-1 protein, mouse ; ALDH1B1 protein, mouse (EC 1.2.1.3) |
Language | English |
Publishing date | 2024-01-09 |
Publishing country | United States |
Document type | Journal Article |
ZDB-ID | 2417226-1 |
ISSN | 1937-9145 ; 1945-0877 |
ISSN (online) | 1937-9145 |
ISSN | 1945-0877 |
DOI | 10.1126/scisignal.adf8016 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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