Masking of retroviral envelope functions by oligomerizing polypeptide adaptors

Frances J. Morling, Kah-Whye Peng, François Loïc Cosset, Stephen J Russell

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)51-61
Number of pages11
JournalVirology
Volume234
Issue number1
DOIs
StatePublished - Jul 21 1997
Externally publishedYes

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Peptides
Factor Xa
Peptide Hydrolases
Membrane Glycoproteins
Infection
Moloney murine leukemia virus
Leucine Zippers
CD40 Ligand
Epidermal Growth Factor
Glycoproteins
Genes
polypeptide C
ecotropic murine leukemia virus receptor

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Masking of retroviral envelope functions by oligomerizing polypeptide adaptors. / Morling, Frances J.; Peng, Kah-Whye; Cosset, François Loïc; Russell, Stephen J.

In: Virology, Vol. 234, No. 1, 21.07.1997, p. 51-61.

Research output: Contribution to journalArticle

Morling, Frances J. ; Peng, Kah-Whye ; Cosset, François Loïc ; Russell, Stephen J. / Masking of retroviral envelope functions by oligomerizing polypeptide adaptors. In: Virology. 1997 ; Vol. 234, No. 1. pp. 51-61.
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