Post-Golgi membrane traffic: brefeldin A inhibits export from distal Golgi compartments to the cell surface but not recycling.

Miller, Stephen G.; Carnell, Lucinda; Moore, Hsiao-Ping

doi:10.1083/jcb.118.2.267

Cited by 199 publications

(123 citation statements)

References 72 publications

(95 reference statements)

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“…Because hRSV F and G glycoproteins use the trans-Golgi network to reach the plasma membrane of hRSV-infected cells, we performed transport inhibition assays with brefeldin A (BFA) to evaluate whether the hRSV N uses a similar pathway to reach the cell surface (34)(35)(36). Based on the virus adsorption experiments described above, the putative mechanism of surface N delivery was explored starting at early infection times (i.e., 24−48 hpi) to reduce noise derived from the attachment of newly released virions that are produced at large amounts from 48 hpi to 72 hpi (Fig.…”

Section: Resultsmentioning

confidence: 99%

Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells

Céspedes

Bueno

Ramírez

et al. 2014

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

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Human respiratory syncytial virus (hRSV) is the leading cause of bronchiolitis and pneumonia in young children worldwide. The recurrent hRSV outbreaks and reinfections are the cause of a significant public health burden and associate with an inefficient antiviral immunity, even after disease resolution. Although several mouse-and human cell-based studies have shown that hRSV infection prevents naïve T-cell activation by antigen-presenting cells, the mechanism underlying such inhibition remains unknown. Here, we show that the hRSV nucleoprotein (N) could be at least partially responsible for inhibiting T-cell activation during infection by this virus. Early after infection, the N protein was expressed on the surface of epithelial and dendritic cells, after interacting with trans-Golgi and lysosomal compartments. Further, experiments on supported lipid bilayers loaded with peptide-MHC (pMHC) complexes showed that surface-anchored N protein prevented immunological synapse assembly by naive CD4 + T cells and, to a lesser extent, by antigen-experienced T-cell blasts. Synapse assembly inhibition was in part due to reduced T-cell receptor (TCR) signaling and pMHC clustering at the T-cell− bilayer interface, suggesting that N protein interferes with pMHC− TCR interactions. Moreover, N protein colocalized with the TCR independently of pMHC, consistent with a possible interaction with TCR complex components. Based on these data, we conclude that hRSV N protein expression at the surface of infected cells inhibits T-cell activation. Our study defines this protein as a major virulence factor that contributes to impairing acquired immunity and enhances susceptibility to reinfection by hRSV.

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Section: Resultsmentioning

confidence: 99%

Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells

Céspedes

Bueno

Ramírez

et al. 2014

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

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“…4C). Brefeldin A is a macrolide antibiotic that has been shown to inhibit vesicle transport to the cell surface, by causing the resorption of the Golgi complex into the endoplasmic reticulum (23)(24)(25). At the concentration of 5 g/ml, brefeldin A did not inhibit protein synthesis in uninfected CEF (compare lanes 1 and 2) and caused only a minor reduction in protein synthesis in avian reovirus-infected cells (compare lanes 5 and 6).…”

Section: Membrane Permeabilization By Avian Reovirus Requires Viral Pmentioning

confidence: 98%

Modification of Late Membrane Permeability in Avian Reovirus-infected Cells

Bodelón

Labrada²,

Martı́nez-Costas

et al. 2002

Journal of Biological Chemistry

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Infection of chicken embryo fibroblasts by avian reovirus induces an increase in the permeability of the host plasma membrane at late, but not early, infection times. The absence of permeability changes at early infection times, as well as the dependence of late membrane modification on both viral protein synthesis and an active exocytic route, suggest that a virus-encoded membrane protein is required for avian reovirus to permeabilize cells. Further studies revealed that expression of nonstructural p10 protein in bacterial cells arrested cell growth and enhanced membrane permeability. Membrane leakiness was also observed following transient expression of p10 in BSC-40 monkey cells. Both its permeabilizing effect and the fact that p10 shares several structural and physical characteristics with other membrane-active viral proteins indicate that p10 is an avian reovirus viroporin. Furthermore, the fusogenic extracellular NH 2 -terminal domain of p10 appears to be dispensable for permeabilizing activity, because its deletion entirely abolished the fusogenic activity of p10, without affecting its ability to associate with cell membranes and to enhance membrane permeability. Similar properties have reported previously for immunodeficiency virus type I transmembrane glycoprotein gp41. Thus, like gp41, p10 appears to be a multifunctional protein that plays key roles in virus-host interaction.Cytolytic viruses induce profound injurious effects in susceptible host cells, resulting in morphological, structural, and biochemical changes and in cell degeneration. A widespread phenomenon during viral infection is the alteration of the permeability of the host plasma membrane (reviewed in Refs.

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“…As a first approach, we utilized BFA. This agent has been shown to disrupt Golgi function and inhibit Golgi-mediated post-translational glycosylation of proteins (21,22). For the experiments shown in Fig.…”

Section: Assessment Of the Steady State Distribution Of Apoe On Thementioning

confidence: 99%

Transport and Processing of Endogenously Synthesized ApoE on the Macrophage Cell Surface

Zhao

Mazzone

2000

Journal of Biological Chemistry

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We have previously established the presence of a pool of apoE sequestered on the macrophage cell surface by demonstrating its displacement from a cell monolayer at 4°C. In this series of experiments, we use a cell surface biotinylation protocol to directly quantitate apoE on the macrophage cell surface and evaluate its transport to and from this cell surface pool. In human monocytederived macrophages labeled to equilibrium and in a mouse macrophage cell line transfected to constitutively express human apoE3, approximately 8% of total cellular apoE was present on the surface, but only a portion of this surface pool served as a direct precursor to secreted apoE. The half-life of apoE on the macrophage cell surface was calculated to be approximately 12 min. On SDS-polyacrylamide gel electrophoresis, the apoE isolated from the surface fraction of cells labeled to equilibrium migrated in an isoform pattern distinct from that observed from the intracellular fraction, with the surface fraction migrating predominantly in a higher molecular weight isoform. Pulse labeling experiments demonstrated that newly synthesized apoE reached the cell surface by 10 min but was predominantly in a low molecular weight isoform. There was also a lag between appearance of apoE on the cell surface and its appearance in the medium. Biotinylated apoE, which accumulated in the medium, even from pulse labeled cells, was predominantly in the high molecular weight isoform. Additional experiments demonstrated that low molecular weight apoE present on the cell surface was modified to higher molecular weight apoE by the addition of sialic acid residues prior to secretion and that this conversion was inhibited by brefeldin A. These results demonstrate an unexpected complexity in the transport and cellular processing of macrophage cell surface apoE. Factors that modulate the size and turnover of the cell surface pool of apoE in the macrophage remain to be identified and investigated.

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Post-Golgi membrane traffic: brefeldin A inhibits export from distal Golgi compartments to the cell surface but not recycling.

Cited by 199 publications

References 72 publications

Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells

Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells

Modification of Late Membrane Permeability in Avian Reovirus-infected Cells

Transport and Processing of Endogenously Synthesized ApoE on the Macrophage Cell Surface

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