PuSH - Publication Server of Helmholtz Zentrum München: Brain endothelial- and epithelial-specific interferon receptor chain 1 drives virus-induced sickness behavior and cognitive impairment.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Blank, T.* ; Detje, C.N.* ; Spieß, A.* ; Hagemeyer, N.* ; Brendecke, S.M.* ; Wolfart, J.* ; Staszewski, O.* ; Zöller, T.* ; Papageorgiou, I.* ; Schneider, J.* ; Paricio-Montesinos, R.* ; Eisel, U.L.* ; Manahan-Vaughan, D.* ; Jansen, S.* ; Lienenklaus, S.* ; Lu, B.* ; Imai, Y.* ; Müller, M.* ; Goelz, S.E.* ; Baker, D.P.* ; Schwaninger, M.* ; Kann, O.* ; Heikenwälder, M. ; Kalinke, U.* ; Prinz, M.*

Brain endothelial- and epithelial-specific interferon receptor chain 1 drives virus-induced sickness behavior and cognitive impairment.

Immunity 44, 901-912 (2016)

Publ. Version/Full Text

DOI

PMC

	Free by publisher

Open Access Green as soon as Postprint is submitted to ZB.

Abstract
Metrics
Extra information

Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR). Using gene profiling, we identified that the endothelia-derived chemokine ligand CXCL10 mediated behavioral changes through impairment of synaptic plasticity. These results identified brain endothelial and epithelial cells as natural gatekeepers for virus-induced sickness behavior, demonstrated tissue specific IFNAR engagement, and established the CXCL10-CXCR3 axis as target for the treatment of behavioral changes during virus infection and type I IFN therapy.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Cxcl10 ; Cxcr3 ; Ifn ; Ifnar1 ; Ips-1 ; Mavs ; Behavior ; Brain ; Depression ; Endothelia ; Epithelia ; Influenza ; Neurons ; Signal Transduction ; Type I Interferon ; Virus Infection; Central-nervous-system; Double-stranded-rna; Long-term Potentiation; Synaptic Plasticity; Major Depression; In-vivo; Rig-i; Mice; Cells; Inflammation

ISSN (print) / ISBN 1074-7613

e-ISSN 1097-4180

Journal Immunity

Quellenangaben Volume: 44, Issue: 4, Pages: 901-912

Publisher Cell Press

Publishing Place Cambridge, Mass.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Virology (VIRO)