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dc.contributor.authorManzetti, J.
dc.contributor.authorWeissbach, F.H.
dc.contributor.authorDrachenberg, C.B.
dc.date.accessioned2020-07-07T19:59:37Z
dc.date.available2020-07-07T19:59:37Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85086856876&doi=10.1016%2fj.isci.2020.101257&partnerID=40&md5=29473289ce8153cbef810a03e6de8e5e
dc.identifier.urihttp://hdl.handle.net/10713/13221
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 CoCl2-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. Copyright 2020 The Author(s)en_US
dc.description.sponsorshipUniversity of Baselen_US
dc.description.urihttps://doi.org/10.1016/j.isci.2020.101257en_US
dc.language.isoen_USen_US
dc.publisherElsevier Inc.en_US
dc.relation.ispartofiScience
dc.subjectBiological Sciencesen_US
dc.subjectCell Biologyen_US
dc.subjectImmunologyen_US
dc.subjectVirologyen_US
dc.titleBK Polyomavirus Evades Innate Immune Sensing by Disrupting the Mitochondrial Network and Promotes Mitophagyen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.isci.2020.101257


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