Nucleocapsid protein of porcine reproductive and respiratory syndrome virus antagonizes the antiviral activity of TRIM25 by interfering with TRIM25-mediated RIG-I ubiquitination.
Porcine reproductive and respiratory syndrome (PRRS) is caused by PRRS virus (PRRSV), and is characterized by respiratory diseases in piglet and reproductive disorders in sow. Identification of sustainable and effective measures to mitigate PRRSV transmission is a pressing problem. The nucleocapsid (N) protein of PRRSV plays a crucial role in ... inhibiting host innate immunity during PRRSV infection. In the current study, a new host-restricted factor, tripartite motif protein 25 (TRIM25), was identified as an inhibitor of PRRSV replication. Co-immunoprecipitation assay indicated that the PRRSV N protein interferes with TRIM25-RIG-I interactions by competitively interacting with TRIM25. Furthermore, N protein inhibits the expression of TRIM25 and TRIM25-mediated RIG-I ubiquitination to suppress interferon ? production. Furthermore, with increasing TRIM25 expression, the inhibitory effect of N protein on the ubiquitination of RIG-I diminished. These results indicate for the first time that TRIM25 inhibits PRRSV replication and that the N protein antagonizes the antiviral activity by interfering with TRIM25-mediated RIG-I ubiquitination. This not only provides a theoretical basis for the development of drugs to control PRRSV replication, but also better explains the mechanism through which the PRRSV N protein inhibits innate immune responses of the host.
Mesh Terms:
Amino Acid Motifs, Animals, Cell Line, Chlorocebus aethiops, DEAD Box Protein 58, HEK293 Cells, Host-Pathogen Interactions, Humans, Immunity, Innate, Nucleocapsid Proteins, Porcine respiratory and reproductive syndrome virus, Protein Binding, RNA, Small Interfering, Signal Transduction, Swine, Transfection, Tripartite Motif Proteins, Ubiquitination, Virus Replication
Amino Acid Motifs, Animals, Cell Line, Chlorocebus aethiops, DEAD Box Protein 58, HEK293 Cells, Host-Pathogen Interactions, Humans, Immunity, Innate, Nucleocapsid Proteins, Porcine respiratory and reproductive syndrome virus, Protein Binding, RNA, Small Interfering, Signal Transduction, Swine, Transfection, Tripartite Motif Proteins, Ubiquitination, Virus Replication
Vet. Microbiol.
Date: Jun. 01, 2019
PubMed ID: 31176400
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