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Peroxisomes are platforms for cytomegalovirus' evasion from the cellular immune response
- Source :
- Scientific Reports, Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP
- Publication Year :
- 2015
-
Abstract
- 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 highjack 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. Fundação para a Ciência e Tecnologia personal fellowships: (SFRH/BPD/77619/2011, SFRH/BPD/103580/2014, SFRH/BD/81223/2011, SFRH/BD/101942/2014); FCT grants: (PTDC-IMI-MIC-0828-2012 - Programa Operacional Temático Factores de Competitividade” (COMPETE) of “Quadro Comunitário de Apoio III”); Fundo Comunitário Europeu (FEDER); BiMED - Institute for Biomedicine grant: (UID/BIM/04501/2013).
- Subjects :
- 0301 basic medicine
Cytomegalovirus
Apoptosis
Mitochondrion
Article
Immediate-Early Proteins
03 medical and health sciences
0302 clinical medicine
Peroxisomes
Humans
Adaptor Proteins, Signal Transducing
Immune Evasion
Immunity, Cellular
Multidisciplinary
biology
Immune evasion
Signal transducing adaptor protein
Membrane Proteins
Hep G2 Cells
Peroxisome
Hedgehog signaling pathway
3. Good health
Transport protein
Cell biology
Mitochondria
Protein Transport
030104 developmental biology
030220 oncology & carcinogenesis
Chaperone (protein)
Cytomegalovirus Infections
biology.protein
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....523146bbc2744bab1fdb093cdb1bf9b3