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dc.contributor.authorGhita, Luca
dc.contributor.authorBreitkopf, Veronika
dc.contributor.authorMulenge, Felix
dc.contributor.authorPavlou, Andreas
dc.contributor.authorGern, Olivia Luise
dc.contributor.authorDurán, Verónica
dc.contributor.authorPrajeeth, Chittappen Kandiyil
dc.contributor.authorKohls, Moritz
dc.contributor.authorJung, Klaus
dc.contributor.authorStangel, Martin
dc.contributor.authorSteffen, Imke
dc.contributor.authorKalinke, Ulrich
dc.identifier.citationJ Neurosci Res. 2021 Jul 23. doi: 10.1002/jnr.24923. Epub ahead of print.en_US
dc.description.abstractTick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, is typically transmitted upon tick bite and can cause meningitis and encephalitis in humans. In TBEV-infected mice, mitochondrial antiviral-signaling protein (MAVS), the downstream adaptor of retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) signaling, is needed to induce early type I interferon (IFN) responses and to confer protection. To characterize the brain-resident cell subset that produces protective IFN-β in TBEV-infected mice, we isolated neurons, astrocytes, and microglia from mice and exposed these cell types to TBEV in vitro. Under such conditions, neurons showed the highest percentage of infected cells, whereas astrocytes and microglia were infected to a lesser extent. In the supernatant (SN) of infected neurons, IFN-β was not detectable, while infected astrocytes showed high and microglia low IFN-β expression. Transcriptome analyses of astrocytes implied that MAVS signaling was needed early after TBEV infection. Accordingly, MAVS-deficient astrocytes showed enhanced TBEV infection and significantly reduced early IFN-β responses. Nevertheless, at later time points, moderate amounts of IFN-β were detected in the SN of infected MAVS-deficient astrocytes. Transcriptome analyses indicated that MAVS deficiency negatively affected the induction of early anti-viral responses, which resulted in significantly increased TBEV replication. Treatment with MyD88 and TRIF inhibiting peptides reduced only late IFN-β responses of TBEV-infected WT astrocytes and blocked entirely IFN-β responses of infected MAVS-deficient astrocytes. Thus, upon TBEV exposure of brain-resident cells, astrocytes are important IFN-β producers showing biphasic IFN-β induction that initially depends on MAVS and later on MyD88/TRIF signaling.en_US
dc.rightsAttribution 4.0 International*
dc.subjectMAVS signalingen_US
dc.subjectastrocytic anti-viral responseen_US
dc.subjectinnate immunityen_US
dc.subjectneurotropic infectionen_US
dc.subjecttick-borne encephalitis virusen_US
dc.titleSequential MAVS and MyD88/TRIF signaling triggers anti-viral responses of tick-borne encephalitis virus-infected murine astrocytes.en_US
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalJournal of neuroscience researchen_US
dc.source.journaltitleJournal of neuroscience research
dc.source.countryUnited States

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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International