Peroxisomes are platforms for cytomegalovirus’ evasion from the cellular immune response
Nature Publishing Group
The human cytomegalovirus developed distinct evasion mechanisms from the cellular antiviral response involving vMIA, a virally-encoded protein that is not only able to prevent cellular apoptosis but also to inhibit signalling downstream from mitochondrial MAVS. vMIA has been shown to localize at mitochondria and to trigger their fragmentation, a phenomenon proven to be essential for the signalling inhibition. Here, we demonstrate that vMIA is also localized at peroxisomes, induces their fragmentation and inhibits the peroxisomal-dependent antiviral signalling pathway. Importantly, we demonstrate that peroxisomal fragmentation is not essential for vMIA to specifically inhibit signalling downstream the peroxisomal MAVS. We also show that vMIA interacts with the cytoplasmic chaperone Pex19, suggesting that the virus has developed a strategy to hijack the peroxisomal membrane proteins’ transport machinery. Furthermore, we show that vMIA is able to specifically interact with the peroxisomal MAVS. Our results demonstrate that peroxisomes constitute a platform for evasion of the cellular antiviral response and that the human cytomegalovirus has developed a mechanism by which it is able to specifically evade the peroxisomal MAVS-dependent antiviral signalling.
This work was financially supported by personal fellowship grants from the Portuguese Foundation for Science and Technology (FCT), ref. SFRH/BPD/77619/2011 (for DR), ref SFRH/BPD/103580/2014 for ARF, ref SFRH/BD/81223/2011 for AG and ref SFRH/BD/101942/2014 for IV, as well as by the FCT grant ref. PTDC-IMI-MIC-0828-2012 under the scope of “Programa Operacional Temático Factores de Competitividade” (COMPETE) of “Quadro Comunitário de Apoio III” and co-financed by Fundo Comunitário Europeu FEDER. The authors would like to thank the iBiMED - Institute for Biomedicine (UID/BIM/04501/2013) for their support.
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.
Scientific Reports 6, Article number: 26028 (2016)