Virus entry and replication in the brain precedes blood-brain barrier disruption during intranasal alphavirus infection

Journal of Neuroimmunology
Matthew D CainRobyn S Klein

Abstract

Viral infections of the central nervous system (CNS) are often associated with blood-brain barrier (BBB) disruption, yet the impact of virus replication and immune cell recruitment on BBB integrity are incompletely understood. Using two-photon microscopy, we demonstrate that Venezuelan equine encephalitis virus (VEEV) strain TC83-GFP, a GFP expressing, attenuated strain with a G3A mutation within the 5' UTR that is associated with increased sensitivity to type I interferons (IFNs), does not directly impact BBB permeability. Following intranasal infection of both wild-type and IFN-induced protein with tetratricopeptide repeats 1 (IFIT1)-deficient mice, which fail to block TC83-specific RNA translation, virus spreads to the olfactory bulb and cortex via migration along axonal tracts of neurons originating from the olfactory neuroepithelium. Global dissemination of virus in the CNS by 2days post-infection (dpi) was associated with increased BBB permeability in the olfactory bulb, but not in the cortex or hindbrain, where permeability only increased after the recruitment of CX3CR1+ and CCR2+ mononuclear cells on 6 dpi, which corresponded with tight junction loss and claudin 5 redistribution. Importantly, despite higher levels of vi...Continue Reading

Citations

Jun 22, 2017·Immunity·Robyn S Klein, Christopher A Hunter
Apr 27, 2019·Annual Review of Immunology·Robyn S KleinMatthew Cain
Apr 3, 2020·JAMA Otolaryngology-- Head & Neck Surgery·Kawinyarat JitaroonZara M Patel
Dec 25, 2019·Journal of Neurovirology·Chunjuan WangShougang Guo
Jun 14, 2019·Frontiers in Aging Neuroscience·Vijayasree V GiridharanTatiana Barichello
Jan 12, 2019·Frontiers in Microbiology·Lindsay LundbergKylene Kehn-Hall
Oct 18, 2019·Frontiers in Microbiology·Ana Rachel LedaMichal Toborek
Aug 29, 2018·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Victoria K Baxter, Mark T Heise
Mar 7, 2020·Frontiers in Immunology·Mohanraj ManangeeswaranDaniela Verthelyi
Aug 24, 2019·Trends in Immunology·Katelynn A Milora, Glenn F Rall
Jun 9, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Stuart WoodsRiccardo V D'Elia

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier & Cytokines

Some cytokines are able to cross the blood brain barrier through transport systems and enter the cerebrospinal fluid and interstitial fluid spaces. Here is the latest research on cytokines crossing the blood brain barrier and how this can affect tissues within the CNS.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.