Sequential MAVS- and MyD88/TRIF-signaling triggers anti-viral responses of tick-borne encephalitis virus-infected murine astrocytes

BioRxiv : the Preprint Server for Biology
L. GhitaUlrich Kalinke

Abstract

Tick-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-like receptor (RLR)-signaling, is needed to induce early type I interferon (IFN) responses and to confer protection. To identify the brain resident cell subset that produces protective IFN-{beta} in TBEV infected mice, we isolated neurons, astrocytes and microglia and exposed these cells 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-{beta} was not detectable, while infected astrocytes showed very high and microglia low IFN-{beta} production. 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-{beta} responses. At later time points, moderate amounts of IFN-{beta} were detected in the SN of infected MAVS-deficient ast...Continue Reading

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