4.8 Article

PLAAT1 inhibits type I interferon response via degradation of IRF3 and IRF7 in Zebrafish

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.979919

Keywords

PLAAT1; IRF3; IRF7; interferon; autophagy; virus

Categories

Funding

  1. National Key R&D Program of China
  2. National Natural Science Foundation of China
  3. Key Laboratory of Marine Biotechnology of Fujian Province
  4. [2018YFD0900302]
  5. [32030112]
  6. [U21A20268]
  7. [2021MB01]

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PLAAT1 plays important roles in tumor suppression, transglutaminase activation, and peroxisomal biogenesis. This study shows that PLAAT1 inhibits the production of type I interferon and promotes virus replication in zebrafish. Mechanistically, PLAAT1 interacts with IRF3 and IRF7 to degrade them.
PLAAT1 is a member of the PLAAT protein family and plays important roles in tumor suppression, transglutaminase activation and peroxisomal biogenesis. Recently, PLAAT1 has been shown to promote degradation of p53 protein and cellular organelles such as mitochondria, endoplasmic reticulum and lysosome. In this study, we show that PLAAT1 inhibits the production of type I interferon and promotes virus replication in zebrafish. Overexpression of Plaat1 in zebrafish cells suppresses antiviral responses and promotes virus replication. Mechanistically, PLAAT1 interacts with IRF3 and IRF7 to initiate degradation of IRF3 and IRF7, which can be attenuated by 3-methyladenine, an inhibitor of autophagosome. Our study provides novel insights into the functions of PLAAT1 in host immune response to viral infection.

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