Improvement of retroviral retargeting by using amino acid spacers between an additional binding domain and the N terminus of Moloney murine leukemia virus SU
Improvement of retroviral retargeting by using amino acid spacers between an additional binding domain and the N terminus of Moloney murine leukemia virus SU
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DOI：
10.1128/jvi.70.3.2059-2064.1996
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发表时间：
1996-03
影响因子：
5.4
通讯作者：
S. Valsesia-Wittmann;F. Morling;B. Nilson;Y. Takeuchi;S. Russell;F. Cosset
中科院分区：
文献类型：
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作者：
S. Valsesia-Wittmann;F. Morling;B. Nilson;Y. Takeuchi;S. Russell;F. Cosset
我们之前报道了一种通过表达单链抗体（S. J. Russell， R. E. Hawkins, and G. Winter, Nucleic Acids Res. 21:1081-1085, 1993）或配体（F.-L.）重定向逆转录病毒宿主范围的策略。陈晓明，陈晓明，陈晓明，陈晓明，等。鼠白血病病毒（MoMLV）表面蛋白（SU）的N端分析。虽然这种嵌合包膜能够结合新的受体，但重靶向病毒的转导效率通常较低。我们假设包膜糖蛋白的构象重排在结合后并没有被最佳地触发，为了克服这些结合后阻滞，我们在这里生成了一组嵌合的MoMLV衍生包膜，针对Ram-1磷酸转运体，我们改变了Ram-1结合域和MoMLV SU之间的间距。所有重组包膜都在病毒粒子上正确表达，并且都有效地与Ram-1结合。然而，结构域间的间隔极大地影响了逆转录病毒载体通过其嵌合包膜结合到Ram-1上的基因转移效率。与我们之前的结果相比，最佳的域间间隔允许通过Ram-1增加100倍的病毒转导。
We previously reported a strategy to redirect the retroviral host range by expressing single-chain antibodies (S. J. Russell, R. E. Hawkins, and G. Winter, Nucleic Acids Res. 21:1081-1085, 1993) or ligands (F.-L. Cosset, F. J Morling, Y. Takeuchi, R. A. Weiss, M. K. L. Collins, and S. J. Russell, J. Virol. 69:6314-6322, 1995) at the N terminus of Moloney murine leukemia virus (MoMLV) surface proteins (SU). Although such chimeric envelopes were able to bind the new receptors, the transduction efficiency of retargeted viruses was generally low. We hypothesized that conformational rearrangements of envelope glycoproteins were not optimally triggered following binding, and to overcome these postbinding blocks, we have generated here a set of chimeric MoMLV-derived envelopes targeted to the Ram-1 phosphate transporter in which we have varied the spacing between the Ram-1-binding domain and the MoMLV SU. All of the recombinant envelopes were correctly expressed on virions, and all bound efficiently to Ram-1. However, the interdomain spacing greatly affected the efficiency of gene transfer by retroviral vectors that had bound to Ram-1 via their chimeric envelopes. Optimal interdomain spacing allowed a 100-fold-increased viral transduction via Ram-1 compared to our previous results.