3 years ago

Paramyxovirus V proteins interact with the RIG-I/TRIM25 regulatory complex and inhibit RIG-I signaling.

Megan L Shaw, Maria T Sanchez-Aparicio, Adolfo García-Sastre, Leighland J Feinman
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 the 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 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 MAVS. 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.

Publisher URL: http://doi.org/10.1128/JVI.01960-17

DOI: 10.1128/JVI.01960-17

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