Mouse Adenovirus Type 1-Induced Breakdown of the Blood-Brain Barrier

Gralinski, Lisa E.; Ashley, Shanna L.; Dixon, Shandee D.; Spindler, Katherine R.

doi:10.1128/jvi.00954-09

Cited by 64 publications

(84 citation statements)

References 85 publications

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“…For instance, there is a lower concentration of antibodies in the brain than in serum. In this regard, the breakdown of the blood-brain barrier mediated by MAV-1 may be significant because it might contribute to the susceptibility of the virus to antibodies (18). It is also noteworthy that the deletion of Trim21 does not impair the survival of C57BL/6 mice to the same degree as ablating antibodies all together, as in the Btk −/− mouse (7).…”

Section: Discussionmentioning

confidence: 91%

Intracellular antibody receptor TRIM21 prevents fatal viral infection

Vaysburd

Watkinson

Cooper

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Host species have evolved mechanisms that can inhibit pathogen replication even after a cell has been successfully invaded. Here we show that tripartite-motif protein 21 (TRIM21), a ubiquitously expressed E3 ubiquitin ligase that targets viruses inside the cytosol, protects mice against fatal viral infection. Upon infection with mouse adenovirus-1, naive mice lacking TRIM21 succumb to encephalomyelitis within 7 d. In contrast, wild-type mice rapidly up-regulate TRIM21 and control viremia. Trim21 heterozygous mice have a haploinsufficiency phenotype in which reduced TRIM21 expression leads to a viral load that is higher than wild types but lower than knockouts. TRIM21 is a high-affinity antibody receptor that allows antibodies to operate inside an infected cell. In passive transfer experiments at high viral dose, antisera that fully protects wild-type mice fails to protect most Trim21 knockout animals. These results demonstrate that TRIM21 provides potent antiviral protection and forms an important part of the humoral immune response.

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Section: Discussionmentioning

confidence: 91%

Intracellular antibody receptor TRIM21 prevents fatal viral infection

Vaysburd

Watkinson

Cooper

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Disruption of the endothelial tight junction transmembrane proteins CLN-3, CLN-5, and OCLN correlates with BBB opening in EAE (4,12), and downregulation of CLN-5 is linked to BBB breakdown in glioblastoma multiforme (50) and models of amyotrophic lateral sclerosis (51) and viral encephalomyelitis (52). Redistribution of CLN-5 and OCLN away from the cell membrane has also been implicated in BBB disruption in inflammatory models (53).…”

Section: Discussionmentioning

confidence: 99%

Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease

Argaw¹,

et al. 2012

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“…Although astrocytes were once thought to serve a structural role in the BBB, it is now clear that they play an important role in maintaining its functional integrity. In vitro, cocultures of brain endothelial cells and astrocytes establish a tighter barrier than endothelial cells alone, and secretion and activation of matrix metalloproteases (MMPs) by astrocytes result in disruption of the BBB during disease (5,6). Astrocytes also modulate neuronal health and activity through the uptake of excess neurotransmitters and secretion of nutrients (7)(8)(9)(10).…”

mentioning

confidence: 99%

Differential Replication of Pathogenic and Nonpathogenic Strains of West Nile Virus within Astrocytes

Hussmann

Samuel

Kim

et al. 2013

J Virol

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The severity of West Nile virus (WNV) infection in immunocompetent animals is highly strain dependent, ranging from avirulent to highly neuropathogenic. Here, we investigate the nature of this strain-specific restriction by analyzing the replication of avirulent (WNV-MAD78) and highly virulent (WNV-NY) strains in neurons, astrocytes, and microvascular endothelial cells, which comprise the neurovascular unit within the central nervous system (CNS). We demonstrate that WNV-MAD78 replicated in and traversed brain microvascular endothelial cells as efficiently as WNV-NY. Likewise, similar levels of replication were detected in neurons. Thus, WNV-MAD78's nonneuropathogenic phenotype is not due to an intrinsic inability to replicate in key target cells within the CNS. In contrast, replication of WNV-MAD78 was delayed and reduced compared to that of WNV-NY in astrocytes. The reduced susceptibility of astrocytes to WNV-MAD78 was due to a delay in viral genome replication and an interferon-independent reduction in cell-to-cell spread. Together, our data suggest that astrocytes regulate WNV spread within the CNS and therefore are an attractive target for ameliorating WNV-induced neuropathology.

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Mouse Adenovirus Type 1-Induced Breakdown of the Blood-Brain Barrier

Cited by 64 publications

References 85 publications

Intracellular antibody receptor TRIM21 prevents fatal viral infection

Intracellular antibody receptor TRIM21 prevents fatal viral infection

Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease

Differential Replication of Pathogenic and Nonpathogenic Strains of West Nile Virus within Astrocytes

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