Gamma Interferon Alters Junctional Integrity via Rho Kinase, Resulting in Blood-Brain Barrier Leakage in Experimental Viral Encephalitis

MBio
Stephanie BonneyJulie A Siegenthaler

Abstract

Blood-brain barrier (BBB) breakdown is a hallmark of many diseases of the central nervous system (CNS). Loss of BBB integrity in CNS diseases such as viral encephalitis results in the loss of nutrient/oxygen delivery, rapid infiltration of immune cells, and brain swelling that can exacerbate neuronal injury. Despite this, the cellular and molecular mechanisms that underlie BBB breakdown in viral encephalitis are incompletely understood. We undertook a comprehensive analysis of the cellular and molecular signaling events that induce BBB breakdown in an experimental model of virus-induced encephalitis in which neonatal mice are infected with reovirus (serotype 3 strain Abney). We show that BBB leakage during reovirus infection correlates with morphological changes in the vasculature, reductions in pericytes (BBB supporting cells), and disorganization of vascular junctions. Pathway analysis on RNA sequencing from brain endothelial cells identified the activation of interferon (IFN) signaling within the brain vasculature following reovirus infection. Our in vitro and in vivo studies show that type II IFN mediated by IFN-γ, a well known antiviral signal, is a major contributor to BBB leakage during reovirus infection. We show that I...Continue Reading

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Citations

Jul 8, 2020·International Journal of Molecular Sciences·Olga Bondareva, Bilal N Sheikh
Oct 6, 2020·Frontiers in Endocrinology·Fu GuiYulan Zhang
Aug 11, 2020·Current Tropical Medicine Reports·Amy Y VittorSteven T DeKosky
Oct 8, 2020·International Journal of Molecular Sciences·Neil A MabbottDavid S Donaldson
Jan 5, 2021·Frontiers in Immunology·Juliane GustCameron J Turtle
Aug 20, 2020·The Journal of Infectious Diseases·Christophe GuervillyFrançoise Dignat-George
Dec 15, 2020·Future Science OA·Fahad Hassan ShahMuhammad Yasir Akbar
Mar 17, 2021·Clinical Reviews in Allergy & Immunology·Márta L DebreczeniLászló Cervenak
Jul 20, 2021·Frontiers in Cellular Neuroscience·Julia DerkJulie A Siegenthaler
Nov 16, 2021·Frontiers in Cellular Neuroscience·Adonis SferaZisis Kozlakidis

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Methods Mentioned

BETA
GTPase
RNA-seq
GTPases
Fluorescence
Flow Cytometry
fluorescence-activated cell sorting
PCR
ELISA
enzyme-linked immunosorbent assay

Software Mentioned

Nikon
Cufflinks
Zen
ImageJ
GraphPad Prism
gSNAP
R

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