Masking of Retroviral Envelope Functions by Oligomerizing Polypeptide Adaptors
| Autor: | Stephen J. Russell, Kah Whye Peng, François-Loïc Cosset, Frances Joanne Morling |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Gene Expression Regulation
Viral Leucine zipper CD40 Ligand Molecular Sequence Data Gene delivery Cleavage (embryo) Mice Viral Envelope Proteins Epidermal growth factor Virology Murine leukemia virus Animals Phosphate Transport Proteins Amino Acid Sequence Receptor chemistry.chemical_classification Recombination Genetic Binding Sites Membrane Glycoproteins biology Symporters Sodium-Phosphate Cotransporter Proteins Type III Membrane Proteins Sodium-Phosphate Cotransporter Proteins 3T3 Cells biology.organism_classification Cell biology Biochemistry chemistry Factor Xa Receptors Virus Moloney murine leukemia virus Glycoprotein Carrier Proteins Peptides Oligopeptides Binding domain |
| Zdroj: | Virology. 234(1):51-61 |
| ISSN: | 0042-6822 |
| DOI: | 10.1006/viro.1997.8628 |
| Popis: | We have constructed chimeric retroviral envelopes displaying N-terminal polypeptides that are known to form homotrimeric associations. The amphotropic receptor (RAM-1) binding domain from the trimeric surface (SU) glycoprotein of 4070A murine leukemia virus (MLV)-inhibited ecotropic receptor (Rec-1) mediated infection by the SU glycoprotein of Moloney MLV when grafted to its N-terminus. The block to Rec-1-mediated infection was reversed when the RAM-1 binding domain was cleaved from the vector particles using an engineered factor Xa protease-sensitive cleavage signal between the envelope glycoprotein and its N-terminal extension. Trimeric leucine zipper peptides and the trimeric C-terminal domain of CD40 ligand were shown to inhibit RAM-1-mediated infection of NIH3T3 cells by the 4070A envelope when fused to its N-terminus, whereas monomeric helical peptides and the monomeric epidermal growth factor domain did not. The block to RAM-1-mediated infection was reversed when the trimeric polypeptides were cleaved from the vector particles by addition of factor Xa protease. Envelope binding assays using cleaved and uncleaved chimeric 4070A envelopes revealed that binding to RAM-1 receptors on mammalian cells was hindered by trimeric, but not by monomeric, N-terminal polypeptides. These results have important implications for the design of protease-activatable vectors for targeted gene delivery. |
| Databáze: | OpenAIRE |
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