A proline-rich motif downstream of the receptor binding domain modulates conformation and fusogenicity of murine retroviral envelopes

Dimitri Lavillette, Marielle Maurice, Catherine Roche, Stephen J Russell, Marc Sitbon, F. L. Cosset

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

The entry of retroviruses into cells depends on receptor recognition by the viral envelope surface subunit SU followed by membrane fusion, which is thought to be mediated by a fusion peptide located at the amino terminus of the envelope transmembrane subunit TM. Several fusion determinants have been previously identified in murine leukemia virus (MLV) envelopes, but their functional interrelationships as well as the processes involved in fusion activation upon retroviral receptor recognition remain unelucidated. Despite both structural and functional similarities of their envelope glycoproteins, ecotropic and amphotropic MLVs display two different postbinding properties: (i) while amphotropic MLVs fuse the cells at neutral pH, penetration of ecotropic MLVs is relatively acid pH dependent and (ii) ecotropic envelopes are more efficient than amphotropic envelopes in inducing cell-to-cell fusion and syncytium formation. By exploiting the latter characteristic in the analysis of chimeras of ecotropic and amphotropic MLV envelopes, we show here that substitution of the ecotropic MLV proline-rich region (PRR), located in the SU between the amino-terminal receptor binding domain and the TM- interacting SU carboxy-terminal domains, is sufficient to revert the amphotropic low-fusogenic phenotype into a high-fusogenic one. Furthermore, we have identified potential β-turns in the PRR that control the stability of SU-TM associations as well as the thresholds required to trigger either cell-to-cell or virus-to-cell fusion. These data, demonstrating that the PRR functions as a signal which induces envelope conformational changes leading to fusion, have enabled us to derive envelopes which can infect cells harboring low levels of available amphotropic receptors.

Original languageEnglish (US)
Pages (from-to)9955-9965
Number of pages11
JournalJournal of Virology
Volume72
Issue number12
StatePublished - Dec 1998
Externally publishedYes

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Proline
proline
Murine leukemia virus
Murine Leukemia Viruses
receptors
mice
cell fusion
Cell Fusion
cells
Retroviridae
Membrane Fusion
chimerism
giant cells
Giant Cells
glycoproteins
Glycoproteins
peptides
Viruses
Phenotype
phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

A proline-rich motif downstream of the receptor binding domain modulates conformation and fusogenicity of murine retroviral envelopes. / Lavillette, Dimitri; Maurice, Marielle; Roche, Catherine; Russell, Stephen J; Sitbon, Marc; Cosset, F. L.

In: Journal of Virology, Vol. 72, No. 12, 12.1998, p. 9955-9965.

Research output: Contribution to journalArticle

Lavillette, Dimitri ; Maurice, Marielle ; Roche, Catherine ; Russell, Stephen J ; Sitbon, Marc ; Cosset, F. L. / A proline-rich motif downstream of the receptor binding domain modulates conformation and fusogenicity of murine retroviral envelopes. In: Journal of Virology. 1998 ; Vol. 72, No. 12. pp. 9955-9965.
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