title: Peroxisomes are platforms for cytomegalovirus' evasion from the cellular immune response.
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.
authors.affiliation: Institute for Research in Biomedicine - iBiMED, Department of Medical Sciences &Department of Biology, University of Aveiro, Aveiro, Portugal.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Magalhães
authors.affiliation: Institute for Research in Biomedicine - iBiMED, Department of Medical Sciences &Department of Biology, University of Aveiro, Aveiro, Portugal.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Ferreira
authors.affiliation: Institute for Research in Biomedicine - iBiMED, Department of Medical Sciences &Department of Biology, University of Aveiro, Aveiro, Portugal.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Gomes
authors.affiliation: Institute for Research in Biomedicine - iBiMED, Department of Medical Sciences &Department of Biology, University of Aveiro, Aveiro, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Vieira
authors.affiliation: Institute for Research in Biomedicine - iBiMED, Department of Medical Sciences &Department of Biology, University of Aveiro, Aveiro, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Gouveia
authors.affiliation: Institute for Research in Biomedicine - iBiMED, Department of Medical Sciences &Department of Biology, University of Aveiro, Aveiro, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Valença
authors.affiliation: Neuroanatomy, Center for Biomedicine and Medical Technology Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Islinger
authors.affiliation: Infections and Immunity Laboratory, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Rute
authors.initials: R
authors.lastname: Nascimento
authors.affiliation: College of Life and Environmental Sciences, Biosciences, University of Exeter, Exeter, Devon, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Schrader
authors.affiliation: Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Kagan
authors.affiliation: Institute for Research in Biomedicine - iBiMED, Department of Medical Sciences &Department of Biology, University of Aveiro, Aveiro, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ribeiro
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017209:Apoptosis; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D056945:Hep G2 Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D057131:Immune Evasion; D007111:Immunity, Cellular; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017874:Immediate-Early Proteins; C505371:MAVS protein, human; D008565:Membrane Proteins; C420323:UL37 protein, Human herpesvirus 5; C087343:PEX19 protein, human