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| The EMBO Journal
(1997) 16, 1214–1223, doi:10.1093/emboj/16.6.1214 |
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| Receptor co-operation in retrovirus entry: recruitment of an auxiliary entry mechanism after retargeted binding |
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| Sandrine Valsesia-Wittmann1, Frances J. Morling2, Theodora Hatziioannou1, Stephen J. Russell2 and François-Loïc Cosset1 |
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1 Centre de Génétique Moléculaire et Cellulaire, CNRS UMR5534, UCB Lyon-I, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France 2 Cambridge Centre for Protein Engineering, MRC Centre, Hills Road, Cambridge CB2 2QH, UK Received 1 November 1996; Revised 9 December 1996. |
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| Abstract |
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| We have constructed Moloney murine leukemia virus (MoMLV)-derived envelope glycoproteins (AMO) displaying an amino-terminal Ram-1-binding domain in which a variety of different amino acid spacers have been inserted between the displayed domain and the MoMLV surface (SU) subunit. Titres of retroviruses generated with these chimeric envelopes were enhanced on cells expressing both Ram-1 and Rec-1 receptors compared with the titres on cells expressing only one or other receptor type. The absolute viral titres and the degree of titre enhancement due to receptor co-operativity were highly variable between the different chimeric envelopes and were determined primarily by the properties of the interdomain spacer. An extreme example of receptor co-operativity was encountered when testing Ram-1-targeted AMOPRO envelopes with specific proline-rich interdomain spacers. AMOPRO viruses could not enter cells expressing only Rec–1 or only Ram-1 but could efficiently infect cells co-expressing both receptors. The data are consistent with a model for receptor co-operativity in which binding to the targeted (Ram-1) receptor triggers conformational rearrangements of the envelope that lead to complete unmasking of the hidden Rec-1-binding domain, thereby facilitating its interaction with the viral (Rec–1) receptor which leads to optimal fusion triggering. |
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| Keywords: glycoprotein, murine leukemia virus, receptors, retrovirus, targeting |
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