Pathway of vesicular stomatitis virus entry leading to infection

Matlin, Karl S.; Reggio, Hubert; Helenius, Ari; Simons, Kai

doi:10.1016/0022-2836(82)90269-8

Cited by 363 publications

(314 citation statements)

References 43 publications

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“…To check for selectivity of the observed inhibition of HIV-1 fusion by purinergic receptor antagonists, we assessed their effects on low pH-dependent fusion mediated by the VSV G glycoprotein. 74 This glycoprotein directs viral entry and fusion through an endosomal pathway. Fusion of pseudoviruses bearing VSV G (referred to as VSVpp) was largely unaffected by purinergic inhibitors, except for a modest (ca.…”

Section: Inhibitors Of P2x1 Receptor Interfere With Hiv-1 Fusionmentioning

confidence: 99%

High-Throughput HIV–Cell Fusion Assay for Discovery of Virus Entry Inhibitors

Marin

Giroud

et al. 2015

ASSAY and Drug Development Technologies

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HIV-1 initiates infection by merging its envelope membrane with the target cell membrane, a process that is mediated by the viral Env glycoprotein following its sequential binding to CD4 and coreceptors, CXCR4 or CCR5. Although HIV-1 fusion has been a target for antiviral therapy, the virus has developed resistance to drugs blocking the CCR5 binding or Env refolding steps of this process. This highlights the need for novel inhibitors. Here, we adapted and optimized an enzymatic HIV-cell fusion assay, which reports the transfer of virus-encapsulated b-lactamase into the cytoplasm, to high-throughput screening (HTS) with a 384-well format. The assay was robustly performed in HTS format and was validated by the pilot screen of a small library of pharmacologically active compounds. Several hits identified by screening included a prominent cluster of purinergic receptor antagonists. Functional studies demonstrated that P2X1 receptor antagonists selectively inhibited HIV-1 fusion without affecting the fusion activity of an unrelated virus that enters cells through an endocytic route. The inhibition of HIV-cell fusion by P2X1 antagonists was not through downmodulation of the cell surface expression of CD4 or coreceptors, thus implicating P2X1 receptor in the HIV-1 fusion step. The ability of these antagonists to inhibit viruses regardless of their coreceptor (CXCR4 or CCR5) preference indicates that fusion is blocked at a late step downstream of coreceptor binding. A future large-scale screening campaign for HIV-1 fusion inhibitors, using the above functional readout, will likely reveal novel classes of inhibitors and suggest potential targets for antiviral therapy.

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Section: Inhibitors Of P2x1 Receptor Interfere With Hiv-1 Fusionmentioning

confidence: 99%

High-Throughput HIV–Cell Fusion Assay for Discovery of Virus Entry Inhibitors

Marin

Giroud

et al. 2015

ASSAY and Drug Development Technologies

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“…Both the cell recognition and the fusion reaction are mediated by the surface glycoprotein G (15)(16)(17)(18)(19).…”

Section: Entry Of Rhabdoviruses Into Host Cellsmentioning

confidence: 99%

Viral membrane fusion: is glycoprotein G of rhabdoviruses a representative of a new class of viral fusion proteins?

Poian

Carneiro

Stauffer

2005

Braz J Med Biol Res

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Enveloped viruses always gain entry into the cytoplasm by fusion of their lipid envelope with a cell membrane. Some enveloped viruses fuse directly with the host cell plasma membrane after virus binding to the cell receptor. Other enveloped viruses enter the cells by the endocytic pathway, and fusion depends on the acidification of the endosomal compartment. In both cases, virus-induced membrane fusion is triggered by conformational changes in viral envelope glycoproteins. Two different classes of viral fusion proteins have been described on the basis of their molecular architecture. Several structural data permitted the elucidation of the mechanisms of membrane fusion mediated by class I and class II fusion proteins. In this article, we review a number of results obtained by our laboratory and by others that suggest that the mechanisms involved in rhabdovirus fusion are different from those used by the two well-studied classes of viral glycoproteins. We focus our discussion on the electrostatic nature of virus binding and interaction with membranes, especially through phosphatidylserine, and on the reversibility of the conformational changes of the rhabdovirus glycoprotein involved in fusion. Taken together, these data suggest the existence of a third class of fusion proteins and support the idea that new insights should emerge from studies of membrane fusion mediated by the G protein of rhabdoviruses. In particular, the elucidation of the three-dimensional structure of the G protein or even of the fusion peptide at different pH's might provide valuable information for understanding the fusion mechanism of this new class of fusion proteins. Correspondence

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“…To investigate membrane recycling routes in epithelial ceils, we implanted the basolateral VSV G protein into the apical membrane of the MDCK cells by low pH-induced fusion (22,47), and followed its fate in the cell during subsequent incubations to find out whether it can be routed to the basolateral membrane. In this paper, we give morphological evidence that implanted G protein is rapidly endocytosed and that some of it is distributed to the basolateral plasma membrane.…”

mentioning

confidence: 99%

Transepithelial transport of a viral membrane glycoprotein implanted into the apical plasma membrane of Madin-Darby canine kidney cells. I. Morphological evidence.

Matlin¹,

Bainton²,

Pesonen³

et al. 1983

The Journal of Cell Biology

104

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The G protein of vesicular stomatitis virus was implanted in the apical plasma membrane of Madin-Darby canine kidney cells by low pH-dependent fusion of the viral envelope with the cellular membrane. The amount of fusion as determined by removal of unfused virions, either by tryptic digestion or by EDTA treatment at 0°C, was 22-24% of the cell-bound virus radioactivity. Upon incubation of cells after implantation, the amount of G protein as detected by immunofluorescence diminished on the apical membrane and appeared within 30 min on the basolateral membrane. At the same time some G protein fluorescence was also seen in intracellular vacuoles. The observations by immunofluorescence were confirmed and extended by electron microscopy. Using immunoperoxidase localization, G protein was seen to move into irregularly shaped vacuoles (endosomes) and multivesicular bodies and to appear on the basolateral plasma membrane. These results suggest that the apical and basolateral domains of Madin-Darby canine kidney cells are connected by an intracellular route.In most cells the plasma membrane is continuously endocytosed (36) and the loss of surface membrane must be balanced by retrieval of membrane from inside the cell. Membrane recycling poses a special problem in epithelial cells because the plasma membrane is polarized; it is divided into apical and basolateral domains with distinct protein and lipid compositions (35). If the plasma membrane is continuously recycling, an important question is how the apical and basolateral domains preserve their unique compositions. If the apical and the basolateral recycling routes are separated, randomization of the cell surface would of course be prevented. If, however, they connect at some point in the cell, continuous sorting of apical and basolateral proteins would have to take place.In an attempt to map the membrane traffic routes to and from the cell surface in epithelial cells, we are using the MadinDarby canine kidney (MDCK) cell line as our experimental system (7, 16). These cells display both structural and functional polarity when grown in culture (24, 32). The microvillar

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Pathway of vesicular stomatitis virus entry leading to infection

Cited by 363 publications

References 43 publications

High-Throughput HIV–Cell Fusion Assay for Discovery of Virus Entry Inhibitors

High-Throughput HIV–Cell Fusion Assay for Discovery of Virus Entry Inhibitors

Viral membrane fusion: is glycoprotein G of rhabdoviruses a representative of a new class of viral fusion proteins?

Transepithelial transport of a viral membrane glycoprotein implanted into the apical plasma membrane of Madin-Darby canine kidney cells. I. Morphological evidence.

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