Viral disruption of the blood–brain barrier

Spindler, Katherine R.; Hsu, Tien

doi:10.1016/j.tim.2012.03.009

Cited by 175 publications

(207 citation statements)

References 94 publications

(127 reference statements)

Supporting

Mentioning

205

Contrasting

Order By: Relevance

“…The BBB is a physical and physiological barrier against the entry of cells and molecules into the CNS (20,22,23), and thus, enhancement of BBB permeability has often been associated with pathological changes in the CNS (19). However, transiently increased BBB permeability has been associated with the clearance of RABV from the CNS and the prevention of rabies (13).…”

Section: Discussionmentioning

confidence: 99%

“…Many host and viral factors contribute to the disruption of BBB integrity (19). In HIV, alteration of occludin and ZO-1 expression at the BBB has been demonstrated to be dependent on viral gp120 and CCL2 (43)(44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

“…The BBB is nonfenestrated to large molecules or xenobiotics, thus providing protection against the invasion of the CNS by macromolecules and microorganisms (19). The BBB is composed of endothelial cells (ECs), pericytes, and astrocytes (20).…”

mentioning

confidence: 99%

“…Alteration of BBB permeability is observed in both bacterial and viral infections. One of the key mechanisms of BBB breakdown is damage to the tight junction (TJ) in the brain microvascular ECs (BMECs) (19). The TJ complex is composed of both transmembrane TJ proteins (occludin and claudins) and cytosolic TJ proteins (zonula occludens-1 [ZO-1]) that link transmembrane TJ proteins to the actin cytoskeleton (21)(22)(23).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Enhancement of Blood-Brain Barrier Permeability and Reduction of Tight Junction Protein Expression Are Modulated by Chemokines/Cytokines Induced by Rabies Virus Infection

Chai

Wen

Zhou

et al. 2014

J Virol

139

134

View full text Add to dashboard Cite

Infection with laboratory-attenuated rabies virus (RABV) enhances blood-brain barrier (BBB) permeability, which has been demonstrated to be an important factor for host survival, since it allows immune effectors to enter the central nervous system (CNS) and clear RABV. To probe the mechanism by which RABV infection enhances BBB permeability, the expression of tight junction (TJ) proteins in the CNS was investigated following intracranial inoculation with laboratory-attenuated or wild-type (wt) RABV. BBB permeability was significantly enhanced in mice infected with laboratory-attenuated, but not wt, RABV. The expression levels of TJ proteins (claudin-5, occludin, and zonula occludens-1) were decreased in mice infected with laboratoryattenuated, but not wt, RABV, suggesting that enhancement of BBB permeability is associated with the reduction of TJ protein expression in RABV infection. RABV neither infects the brain microvascular endothelial cells (BMECs) nor modulates the expression of TJ proteins in BMECs. However, brain extracts prepared from mice infected with laboratory-attenuated, but not wt, RABV reduced TJ protein expression in BMECs. It was found that brain extracts from mice infected with laboratory-attenuated RABV contained significantly higher levels of inflammatory chemokines/cytokines than those from mice infected with wt RABV. Pathway analysis indicates that gamma interferon (IFN-␥) is located in the center of the cytokine network in the RABV-infected mouse brain, and neutralization of IFN-␥ reduced both the disruption of BBB permeability in vivo and the downregulation of TJ protein expression in vitro. These findings indicate that the enhancement of BBB permeability and the reduction of TJ protein expression are due not to RABV infection per se but to virus-induced inflammatory chemokines/cytokines. IMPORTANCEPrevious studies have shown that infection with only laboratory-attenuated, not wild-type, rabies virus (RABV) enhances bloodbrain barrier (BBB) permeability, allowing immune effectors to enter the central nervous system (CNS) and clear RABV from the CNS. This study investigated the mechanism by which RABV infection enhances BBB permeability. It was found that RABV infection enhances BBB permeability by downregulation of tight junction (TJ) protein expression in the brain microvasculature. It was further found that it is not RABV infection per se but the chemokines/cytokines induced by RABV infection that downregulate the expression of TJ proteins and enhance BBB permeability. Blocking some of these cytokines, such as IFN-␥, ameliorated both the disruption of BBB permeability and the downregulation of TJ protein expression. These studies may provide a foundation for developing therapeutics for clinical rabies, such as medication that could be used to enhance BBB permeability.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Enhancement of Blood-Brain Barrier Permeability and Reduction of Tight Junction Protein Expression Are Modulated by Chemokines/Cytokines Induced by Rabies Virus Infection

Chai

Wen

Zhou

et al. 2014

J Virol

139

134

View full text Add to dashboard Cite

show abstract

“…We also observed disruption of the actin cytoskeleton network and that of intercellular junctions as evidenced by the rounding of infected cells. The actin cytoskeleton has an important role in the maintenance of stable inter-endothelial junctions and prevents paracellular transport to the brain (Spindler & Hsu, 2012;Stamatovic et al, 2012). Remodelling of intracellular membranes was the third hallmark of a picornavirus infection seen in infected hCMEC/D3 cells, but discrete variations occurred between echoviruses (E-6, E-12 and E-30) and EV-A71.…”

Section: Impairment Of the Bbb By Enterovirusesmentioning

confidence: 99%

Differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of serotype EV-A71 in crossing an in vitro model of the human blood–brain barrier

Volle

Archimbaud

Couraud

et al. 2015

Journal of General Virology

View full text Add to dashboard Cite

Human cerebral microvascular endothelial cells (hCMEC/D3 cell line) form a steady polarized barrier when cultured in vitro on a permeable membrane. Their susceptibility to enterovirus (EV) strains was analysed to investigate how these viruses may cross the blood-brain barrier. A sample of 88 virus strains was selected on phylogenetic features amongst 43 epidemiologically relevant types of the four EV species A-D. The EV-A71 genome was replicated at substantial rates, whilst the infectious virus was released at extremely low but sustained rates at both barrier sides for at least 4 days. EV-A71 antigens were detected in a limited number of cells. The properties of the endothelial barrier (structure and permeability) remained intact throughout infection. The chronic EV-A71 infection was in sharp contrast to the productive infection of cytolytic EVs (e.g. echoviruses E-6 and E-30). The hCMEC/D3 barriers infected with the latter EVs exhibited elevated proportions of apoptotic and necrotic cells, which resulted in major injuries to the endothelial barriers with a dramatic increase of paracellular permeability and virus crossing to the abluminal side. The following intracellular rearrangements were also seen: early destruction of the actin cytoskeleton, remodelling of intracellular membranes and reorganization of the mitochondrion network in a small cluster near the perinuclear space.

show abstract

The Central Nervous System

2022

Veterinary Head and Neck Imaging

View full text Add to dashboard Cite

Viral disruption of the blood–brain barrier

Cited by 175 publications

References 94 publications

Enhancement of Blood-Brain Barrier Permeability and Reduction of Tight Junction Protein Expression Are Modulated by Chemokines/Cytokines Induced by Rabies Virus Infection

Enhancement of Blood-Brain Barrier Permeability and Reduction of Tight Junction Protein Expression Are Modulated by Chemokines/Cytokines Induced by Rabies Virus Infection

Differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of serotype EV-A71 in crossing an in vitro model of the human blood–brain barrier

The Central Nervous System

Contact Info

Product

Resources

About