Paramyxovirus V Proteins Interact with the RIG-I/TRIM25 Regulatory Complex and Inhibit RIG-I Signaling.
J Virol
; 92(6)2018 03 15.
Article
en En
| MEDLINE
| ID: mdl-29321315
ABSTRACT
Paramyxovirus V proteins are known antagonists of the RIG-I-like receptor (RLR)-mediated interferon induction pathway, interacting with and inhibiting the RLR MDA5. We report interactions between the Nipah virus V protein and both RIG-I regulatory protein TRIM25 and RIG-I. We also observed interactions between these host proteins and the V proteins of measles virus, Sendai virus, and parainfluenza virus. These interactions are mediated by the conserved C-terminal domain of the V protein, which binds to the tandem caspase activation and recruitment domains (CARDs) of RIG-I (the region of TRIM25 ubiquitination) and to the SPRY domain of TRIM25, which mediates TRIM25 interaction with the RIG-I CARDs. Furthermore, we show that V interaction with TRIM25 and RIG-I prevents TRIM25-mediated ubiquitination of RIG-I and disrupts downstream RIG-I signaling to the mitochondrial antiviral signaling protein. This is a novel mechanism for innate immune inhibition by paramyxovirus V proteins, distinct from other known V protein functions such as MDA5 and STAT1 antagonism.IMPORTANCE The host RIG-I signaling pathway is a key early obstacle to paramyxovirus infection, as it results in rapid induction of an antiviral response. This study shows that paramyxovirus V proteins interact with and inhibit the activation of RIG-I, thereby interrupting the antiviral signaling pathway and facilitating virus replication.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Proteínas Virales
/
Replicación Viral
/
Paramyxoviridae
/
Transducción de Señal
/
Infecciones por Paramyxoviridae
/
Ubiquitina-Proteína Ligasas
/
Proteína 58 DEAD Box
/
Proteínas de Motivos Tripartitos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Virol
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos