RNA-binding protein PTENα blocks RIG-I activation to prevent viral inflammation.
Nat Chem Biol
; 20(10): 1317-1328, 2024 Oct.
Article
em En
| MEDLINE
| ID: mdl-38773328
ABSTRACT
A timely inflammatory response is crucial for early viral defense, but uncontrolled inflammation harms the host. Retinoic acid-inducible gene I (RIG-I) has a pivotal role in detecting RNA viruses, yet the regulatory mechanisms governing its sensitivity remain elusive. Here we identify PTENα, an N-terminally extended form of PTEN, as an RNA-binding protein with a preference for the CAUC(G/U)UCAU motif. Using both in vivo and in vitro viral infection assays, we demonstrated that PTENα restricted the host innate immune response, relying on its RNA-binding capacity and phosphatase activity. Mechanistically, PTENα directly bound to viral RNA and enzymatically converted its 5'-triphosphate to 5'-monophosphate, thereby reducing RIG-I sensitivity. Physiologically, brain-intrinsic PTENα exerted protective effects against viral inflammation, while peripheral PTENα restricted host antiviral immunity and, to some extent, promoted viral replication. Collectively, our findings underscore the significance of PTENα in modulating viral RNA- and RIG-I-mediated immune recognition, offering potential therapeutic implications for infectious diseases.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
PTEN Fosfo-Hidrolase
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Proteína DEAD-box 58
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Inflamação
Limite:
Animals
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Humans
Idioma:
En
Revista:
Nat Chem Biol
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Nat. chem. biol
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Nature chemical biology
Assunto da revista:
BIOLOGIA
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QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article