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dc.contributor.authorManzetti, Julia
dc.contributor.authorWeissbach, Fabian H.
dc.contributor.authorGraf, Fabrice E.
dc.contributor.authorUnterstab, Gunhild
dc.contributor.authorWernli, Marion
dc.contributor.authorHopfer, Helmut
dc.contributor.authorDrachenberg, Cinthia B.
dc.contributor.authorRinaldo, Christine Hanssen
dc.contributor.authorHirsch, Hans H.
dc.date.accessioned2021-04-14T12:08:02Z
dc.date.available2021-04-14T12:08:02Z
dc.date.issued2020-06-10
dc.description.abstractImmune escape contributes to viral persistence, yet little is known about human polyomaviruses. BK-polyomavirus (BKPyV) asymptomatically infects 90% of humans but causes premature allograft failure in kidney transplant patients. Despite virus-specific T cells and neutralizing antibodies, BKPyV persists in kidneys and evades immune control as evidenced by urinary shedding in immunocompetent individuals. Here, we report that BKPyV disrupts the mitochondrial network and membrane potential when expressing the 66aa-long agnoprotein during late replication. Agnoprotein is necessary and sufficient, using its amino-terminal and central domain for mitochondrial targeting and network disruption, respectively. Agnoprotein impairs nuclear IRF3-translocation, interferon-beta expression, and promotes p62/SQSTM1-mitophagy. Agnoprotein-mutant viruses unable to disrupt mitochondria show reduced replication and increased interferon-beta expression but can be rescued by type-I interferon blockade, TBK1-inhibition, or CoCl<sub>2</sub>-treatment. Mitochondrial fragmentation and p62/SQSTM1-autophagy occur in allograft biopsies of kidney transplant patients with BKPyV nephropathy. JCPyV and SV40 infection similarly disrupt mitochondrial networks, indicating a conserved mechanism facilitating polyomavirus persistence and post-transplant disease.en_US
dc.identifier.citationManzetti, Weissbach, Graf, Unterstab, Wernli, Hopfer, Drachenberg, Rinaldo, Hirsch. BK polyomavirus evades innate immune sensing by disrupting the mitochondrial network and promotes mitophagy. iScience. 2020;23:101257(7):1-43en_US
dc.identifier.cristinIDFRIDAID 1892132
dc.identifier.doi10.1016/j.isci.2020.101257
dc.identifier.issn2589-0042
dc.identifier.urihttps://hdl.handle.net/10037/20880
dc.language.isoengen_US
dc.publisherCell Pressen_US
dc.relation.journaliScience
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleBK polyomavirus evades innate immune sensing by disrupting the mitochondrial network and promotes mitophagyen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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