Ebola Virus Secretory Glycoprotein (sGP) Diminishes FcγRIIIB-to-CR3 Proximity on Neutrophils

Kindzelskii, Andrei L.; Yang, Zhi Yong; Nabel, Gary J.; Todd, Robert F.; Petty, Howard R.

doi:10.4049/jimmunol.164.2.953

Cited by 66 publications

(51 citation statements)

References 26 publications

(15 reference statements)

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“…Adhesion and accessory proteins such as ␣V are involved in immune cell homing and signaling (2), and down-regulation by GP may further affect homing, acute inflammation, and costimulation that would reduce both innate and acquired immune responses. At the same time, the cytotoxic effects of GP on macrophage and endothelial cell function affect the function of inflammatory cells (10,19) and disrupt the integrity of the vasculature (18). Together, these cytotoxic effects are likely responsible for the inflammatory dysregulation, immune suppression, and vascular dysfunction that are hallmarks of lethal Ebola virus infection.…”

Section: Vol 79 2005 Ebola Virus Toxicity Involves Cellular Trafficmentioning

confidence: 99%

Ebola Virus Glycoprotein Toxicity Is Mediated by a Dynamin-Dependent Protein-Trafficking Pathway

Sullivan

Peterson

Yang

et al. 2005

J Virol

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Ebola virus infection causes a highly lethal hemorrhagic fever syndrome associated with profound immunosuppression through its ability to induce widespread inflammation and cellular damage. Though GP, the viral envelope glycoprotein, mediates many of these effects, the molecular events that underlie Ebola virus cytopathicity are poorly understood. Here, we define a cellular mechanism responsible for Ebola virus GP cytotoxicity. GP selectively decreased the expression of cell surface molecules that are essential for cell adhesion and immune function. GP dramatically reduced levels of ␣V␤3 without affecting the levels of ␣2␤1 or cadherin, leading to cell detachment and death. This effect was inhibited in vitro and in vivo by brefeldin A and was dependent on dynamin, the GTPase. GP also decreased cell surface expression of major histocompatibility complex class I molecules, which alters recognition by immune cells, and this effect was also dependent on the mucin domain previously implicated in GP cytotoxicity. By altering the trafficking of select cellular proteins, Ebola virus GP inflicts cell damage and may facilitate immune escape by the virus.

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Section: Vol 79 2005 Ebola Virus Toxicity Involves Cellular Trafficmentioning

confidence: 99%

Ebola Virus Glycoprotein Toxicity Is Mediated by a Dynamin-Dependent Protein-Trafficking Pathway

Sullivan

Peterson

Yang

et al. 2005

J Virol

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“…Single-cell spectra were obtained using a imaging spectrophotometer system (14,15). Labeled cells were illuminated with an excitation filter at 485DF22 nm and a 510LP dichroic mirror for FITC and resonance energy transfer (RET) experiments.…”

Section: Fluorescence Microscopymentioning

confidence: 99%

“…Long-pass dichroic mirrors at 510 and 560 nm were used for FITC and rhodamine, respectively. For energy transfer imaging, the 485DF22, 510LP, and 590DF30 filter combination was used (14).…”

Section: Fluorescence Microscopymentioning

confidence: 99%

Cutting Edge: Evidence for a Signaling Partnership Between Urokinase Receptors (CD87) and L-Selectin (CD62L) in Human Polymorphonuclear Neutrophils

Sitrin

Pan

Blackwood

et al. 2001

The Journal of Immunology

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Leukocyte urokinase plasminogen activator receptors (uPARs) cluster at adhesion interfaces and at migratory fronts where they participate in adhesion, chemotaxis, and proteolysis. uPAR aggregation triggers activation signaling even though this glycolipid-anchored protein must associate with membrane-spanning proteins to access the cell interior. This study demonstrates a novel partnership between uPAR and L-selectin in human polymorphonuclear neutrophils. Fluorescence resonance energy transfer demonstrated a direct physical association between uPAR and L-selectin. To examine the role of L-selectin in uPAR-mediated signaling, uPAR was cross-linked and intracellular Ca2+ concentrations were measured by spectrofluorometry. A mAb reactive against the carbohydrate binding domain (CBD) of L-selectin substantially inhibited uPAR-mediated Ca2+ mobilization, whereas mAbs against the β2 integrin complement receptor 3 (CR3), another uPAR-binding adhesion protein, had no effect. Similarly, fucoidan, a sulfated polysaccharide that binds to L-selectin CBD, inhibited the Ca2+ signal. We conclude that uPAR associates with the CBD region of L-selectin to form a functional signaling complex.

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“…The function of the protein is not fully understood. A putative role of sGP in immune modulation has been discussed controversially [30][31][32]. Recently, it has been shown to act as an antiinflammatory factor by protecting the endothelial cell barrier function during infection [32].…”

mentioning

confidence: 99%

Filovirus Replication and Transcription

2007

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The highly pathogenic filoviruses, Marburg and Ebola virus, belong to the nonsegmented negative-sense RNA viruses of the order Mononegavirales. The mode of replication and transcription is similar for these viruses. On one hand, the negative-sense RNA genome serves as a template for replication, to generate progeny genomes, and, on the other hand, for transcription, to produce mRNAs. Despite the similarities in the replication/transcription strategy, filoviruses have evolved structural and functional properties that are unique among the nonsegmented negativesense RNA viruses. Moreover, there are also striking differences in the replication and transcription mechanisms of Marburg and Ebola virus. This includes nucleocapsid formation, the structure of the genomic replication promoter, the protein requirement for transcription and the use of mRNA editing. In this article, the current knowledge of the replication and transcription strategy of Marburg and Ebola virus is reviewed, with focus on the observed differences.

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Ebola Virus Secretory Glycoprotein (sGP) Diminishes FcγRIIIB-to-CR3 Proximity on Neutrophils

Cited by 66 publications

References 26 publications

Ebola Virus Glycoprotein Toxicity Is Mediated by a Dynamin-Dependent Protein-Trafficking Pathway

Ebola Virus Glycoprotein Toxicity Is Mediated by a Dynamin-Dependent Protein-Trafficking Pathway

Cutting Edge: Evidence for a Signaling Partnership Between Urokinase Receptors (CD87) and L-Selectin (CD62L) in Human Polymorphonuclear Neutrophils

Filovirus Replication and Transcription

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