PRRSV NSP1α degrades TRIM25 through proteasome system to inhibit host antiviral immune response.
Vet Microbiol
; 296: 110173, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38971119
ABSTRACT
Porcine reproductive and respiratory syndrome (PRRS) is the most economically significant disease caused by porcine reproductive and respiratory syndrome virus (PRRSV). Type I interferon (IFN) induces a large number of interferon-stimulated genes (ISGs) expression to inhibit PRRSV infection. To survive in the host, PRRSV has evolved multiple strategies to antagonize host innate immune response. Previous studies have reported that PRRSV N protein decreases the expression of TRIM25 and TRIM25-mediated RIG-I ubiquitination to suppress IFN-ß production. However, whether other PRRSV proteins inhibit the antiviral function of TRIM25 is less well understood. In this study, we first found that PRRSV NSP1α decreased ISGylation of TRIM25. Meanwhile, NSP1α significantly suppressed TRIM25-mediated IFN-ß production to promote PRRSV replication. Further studies demonstrated that PRRSV NSP1α reduced the protein level of TRIM25 in proteasome system but did not regulate the transcription level of TRIM25. In addition, the function of NSP1α in TRIM25 degradation did not rely on its papain-like cysteine protease activity. Taken together, PRRSV NSP1α antagonizes the antiviral response of TRIM25 by mediating TRIM25 degradation to promote PRRSV replication. Our data identify TRIM25 as a natural target of PRRSV NSP1α and reveal a novel mechanism that PRRSV induces TRIM25 degradation and inhibits host antiviral immune response.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virus Replication
/
Viral Nonstructural Proteins
/
Porcine respiratory and reproductive syndrome virus
/
Ubiquitin-Protein Ligases
/
Proteasome Endopeptidase Complex
/
Tripartite Motif Proteins
/
Immunity, Innate
Limits:
Animals
/
Humans
Language:
En
Journal:
Vet Microbiol
Year:
2024
Document type:
Article
Affiliation country:
China