A Cell Line Expressing Vesicular Stomatitis Virus Glycoprotein Fuses at Low
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Florkiewicz, Robert Z.; Rose, J K

doi:10.1126/science.6087454

Cited by 126 publications

(99 citation statements)

References 18 publications

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“…The mature, trimeric wt G protein catalyzes membrane fusion at pH values <6.2 (Florkiewicz and Rose, 1984;Riedel et al, 1984). Fusion activity is accompanied by a characteristic increase in the stability of the trimer (Doms et al, 1987).…”

Section: Conformation Of the Cytoplasmic Domain Mutantsmentioning

confidence: 99%

Differential effects of mutations in three domains on folding, quaternary structure, and intracellular transport of vesicular stomatitis virus G protein.

Doms

Ruusala

Machamer

et al. 1988

The Journal of Cell Biology

193

148

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Abstract. The vesicular stomatitis virus glycoprotein (G protein) is an integral membrane protein which assembles into noncovalently associated trimers before transport from the endoplasmic reticulum. In this study we have examined the folding and oligomeric assembly of twelve mutant G proteins with alterations in the cytoplasmic, transmembrane, or ectodomains. Through the use of conformation-specific antibodies, we found that newly synthesized G protein folded into a conformation similar to the mature form within 1-3 min of synthesis and before trimer formation. Mutant proteins not capable of undergoing correct initial folding did not trimerize, were not transported, and were found in large aggregates. They had, as a rule, mutations in the ectodomain, including several with altered glycosylation patterns. In contrast, mutations in the cytoplasmic domain generally had little effect on folding and trimerization. These mutant proteins, whose ectodomains were identical to the wild-type by several assays, were either transported to the cell surface slowly or not at all. We concluded that while correct ectodomain folding and trimer formation are prerequisites for transport, they alone are not sufficient. The results suggest that the cytoplasmic domain of the wild-type protein may facilitate rapid, efficient transport from the ER, which can be easily affected or eliminated by tail mutations that do not detectably affect the ectodomain.

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Section: Conformation Of the Cytoplasmic Domain Mutantsmentioning

confidence: 99%

Differential effects of mutations in three domains on folding, quaternary structure, and intracellular transport of vesicular stomatitis virus G protein.

Doms

Ruusala

Machamer

et al. 1988

The Journal of Cell Biology

193

148

View full text Add to dashboard Cite

show abstract

“…The acidification of these endosomes by an ATP-dependent proton pump is responsible for initiating the fusion of viral and cellular membranes (Eidelman et al, 1984;Florkiewicz and Rose, 1984). Recently, computer simulations of the structure of KFT25 and calculations of the hydropathicity and of the mean hydrophobic moment of the KFT25 peptide indicated that the peptide is composed of three distinct structural regions separated by Pro residues: an N-terminal hydrophobic a-helix (Lys-Pro region), a central hydrophilic globular structure (His-Pro region) and a slightly hydrophilic C-terminal 5-structure (Ser-Pro).…”

Section: Viruses and Viral Particlesmentioning

confidence: 99%

Enhancement of immunotoxin activity using chemical and biological reagents

1997

Br J Cancer

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Summary One of the major discoveries of effective therapeutics is the use of targeted treatment, such as antibody-directed toxins, i.e. immunotoxins; however, this medicine delivery strategy is still at a developmental stage. A number of problems need to be resolved; one is their inefficacy when applied in vivo. Research has stimulated interest in this area through the use of chemical reagents and other moieties to increase the activity of immunotoxins. In this article, reagents that can potentiate the cytotoxicity of immunotoxins are reviewed and the mechanisms that increase activity of immunotoxins are discussed. Lysosomotropic amines, especially ammonium chloride and chloroquine, may raise the pH value of the lysosome in which the conjugates enter. Carboxylic ionophores, e.g. monensin, can influence Golgi vacuolation, which may facilitate the routing of conjugates, augmenting activity. Calcium channel antagonists may increase immunotoxin killing through morphological or other mechanisms that are not yet well understood. Viral particles and surface structure can enhance the cytotoxicity of conjugates, probably through the mechanism of disrupting endosomes. In addition, cytokines, 3-adrenergic blockers, immunosuppressive agents (cyclosporin A) and some antibiotics (daunorubicin) can be used to increase the effect of immunotoxins.

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“…In VSV, which belongs to the family Rhabdoviridae, both viral attachment to the host cell as well as membrane fusion in the acidic environment of the endosomal compartment are mediated by the G protein (21)(22)(23). VSV recombinants have been used as vectors in vaccine studies (24,25) and VSV-G for pseudotyping of other enveloped viruses (26,27).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic immune response induced by intratumoral expression of the fusogenic membrane protein of vesicular stomatitis virus and cytokines encoded by adenoviral vectors

Hoffmann¹,

Bayer²,

Wildner

2007

Int J Mol Med

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Abstract.We assessed whether intratumoral expression of the fusogenic membrane protein of vesicular stomatitis virus (VSV-G), encoded by a replication-defective adenovirus vector (Ad.VSV-G), alone or in combination with local coexpression of cytokines induces tumor-specific immune responses in a syngeneic murine colon cancer model. We confirmed in vitro by dye colocalization that transduction of murine cells with Ad.VSV-G induces cell-cell fusion. In a bilateral syngeneic subcutaneous colon cancer model in C57BL/6 and BALB/c mice, we demonstrated that intratumoral injection of Ad.VSV-G leads to a significant growth reduction of the directly vector-treated tumor, but also of the contralateral not directly vector-treated tumor. When compared to monotherapy, the anti-neoplastic efficacy was significantly enhanced when intratumoral Ad.VSV-G administration was combined with adenovirus vectors encoding IL-2, IL-12, IL-18, IL-21, or GM-CSF. The antitumor effects of the first three cytokines in combination with VSV-G expression were somewhat greater than those of the latter two. However, the differences did not reach statistical significance. The combination therapy resulted also in a significantly enhanced survival when compared to monotherapy. In addition, we demonstrated that intratumoral expression of VSV-G in combination with the tested cytokines induced a strong tumor-specific cytotoxic T lymphocyte (CTL) response and infiltration of tumors with macrophages. The effects of the combination therapy were clearly greater than those of the monotherapy. Our experimental data indicate that intratumoral expression of VSV-G, particularly in combination with cytokines, is a promising novel tool for the development of in situ tumor vaccination approaches.

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A Cell Line Expressing Vesicular Stomatitis Virus Glycoprotein Fuses at Low p H

Cited by 126 publications

References 18 publications

Differential effects of mutations in three domains on folding, quaternary structure, and intracellular transport of vesicular stomatitis virus G protein.

Differential effects of mutations in three domains on folding, quaternary structure, and intracellular transport of vesicular stomatitis virus G protein.

Enhancement of immunotoxin activity using chemical and biological reagents

Therapeutic immune response induced by intratumoral expression of the fusogenic membrane protein of vesicular stomatitis virus and cytokines encoded by adenoviral vectors

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