Fowl adenovirus serotype 4 52/55k protein triggers PKR degradation by ubiquitin-proteasome system to evade effective innate immunity.
Vet Microbiol
; 278: 109660, 2023 Mar.
Article
em En
| MEDLINE
| ID: mdl-36657343
ABSTRACT
The pro- and inflammatory cytokines fail to effectively inhibit FAdV-4, which has always puzzled us. In the current study, the data determined that the mRNA levels of interferons were significantly enhanced in the livers and LMH cells from 24 h to 72 h post FAdV-4 infection. But the viral load of FAdV-4 was still significantly increased, which meant that FAdV-4 evaded innate immune response. We additionally revealed that the protein levels not mRNA levels of PKR were degraded in host cell at 48 h post FAdV-4 infection. Moreover, the results of over expression and silent expression of PKR revealed that PKR could inhibit FAdV-4 proliferation. These results indicated that FAdV-4 degraded the protein levels of PKR to evade innate immune response. We also found that the protein degradation levels of PKR induced by FAdV-4 were recovery in LHM cells after treatment with proteasome inhibitor MG132, and ubiquitin-specific proteases inhibitor DUB-IN-1. Furthermore, our current data presented that FAdV-4 52/55 K protein directly interacted with PKR and degraded it determined by Co-immunoprecipitation and immunofluorescence. We also determined that 52/55 K protein triggered PKR degradation, and the degradation of PKR could be recovery in LHM cells after treatment with MG132, or DUB-IN-1, respectively. Finally, our data demonstrated that 52/55 K protein was a ubiquitylase that could directly degrade PKR protein in host cells via the ubiquitin-proteasome pathway. Therefore, the current study firstly revealed that FAdV-4 52/55 K protein played the key role in triggering PKR degradation by ubiquitin-proteasome system pathway to escape from innate immunity response.
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MEDLINE
Assunto principal:
Doenças das Aves Domésticas
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Infecções por Adenoviridae
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Aviadenovirus
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article