A Novel Non-Mammalian-Specific HERC7 Negatively Regulates IFN Response through Degrading RLR Signaling Factors.
J Immunol
; 208(5): 1189-1203, 2022 03 01.
Article
em En
| MEDLINE
| ID: mdl-35101889
ABSTRACT
The small HERC family currently comprises four members (HERC3-6) involved in the regulation of various physiological activities. Little is known about the role of HERCs in IFN response. In this study, we identify a novel fish HERC member, named crucian carp HERC7, as a negative regulator of fish IFN response. Genome-wide search of homologs and comprehensive phylogenetic analyses reveal that the small HERC family, apart from HERC3-6 that have been well-characterized in mammals, contains a novel HERC7 subfamily exclusively in nonmammalian vertebrates. Lineage-specific and even species-specific expansion of HERC7 subfamily in fish indicates that crucian carp HERC7 might be species-specific. In virally infected fish cells, HERC7 is induced by IFN and selectively targets three retinoic acid-inducible gene-I-like receptor signaling factors for degradation to attenuate IFN response by two distinct strategies. Mechanistically, HERC7 delivers mediator of IFN regulatory factor 3 activator and mitochondrial antiviral signaling protein for proteasome-dependent degradation at the protein level and facilitates IFN regulatory factor 7 transcript decay at the mRNA level, thus abrogating cellular IFN induction to promote virus replication. Whereas HERC7 is a putative E3 ligase, the E3 ligase activity is not required for its negative regulatory function. These results demonstrate that the ongoing expansion of the small HERC family generates a novel HERC7 to fine-tune fish IFN antiviral response.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Reoviridae
/
Rhabdoviridae
/
Interferons
/
Ubiquitina-Proteína Ligases
/
Fator Regulador 7 de Interferon
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China