Nei-like DNA glycosylase 2 selectively antagonizes interferon-ß expression upon respiratory syncytial virus infection.
J Biol Chem
; 299(8): 105028, 2023 08.
Article
en En
| MEDLINE
| ID: mdl-37423306
ABSTRACT
As part of the antiviral response, cells activate the expressions of type I interferons (IFNs) and proinflammatory mediators to control viral spreading. Viral infections can impact DNA integrity; however, how DNA damage repair coordinates antiviral response remains elusive. Here we report Nei-like DNA glycosylase 2 (NEIL2), a transcription-coupled DNA repair protein, actively recognizes the oxidative DNA substrates induced by respiratory syncytial virus (RSV) infection to set the threshold of IFN-ß expression. Our results show that NEIL2 antagonizes nuclear factor κB (NF-κB) acting on the IFN-ß promoter early after infection, thus limiting gene expression amplified by type I IFNs. Mice lacking Neil2 are far more susceptible to RSV-induced illness with an exuberant expression of proinflammatory genes and tissue damage, and the administration of NEIL2 protein into the airway corrected these defects. These results suggest a safeguarding function of NEIL2 in controlling IFN-ß levels against RSV infection. Due to the short- and long-term side effects of type I IFNs applied in antiviral therapy, NEIL2 may provide an alternative not only for ensuring genome fidelity but also for controlling immune responses.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Virus Sincitiales Respiratorios
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Interferón beta
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Infecciones por Virus Sincitial Respiratorio
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ADN Glicosilasas
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos