@article{575c742aa9934f12bb6bde74382075d8,
title = "Allosteric induction of the CD4-bound conformation of HIV-1 Gp120",
abstract = "Background: HIV-1 infection of target cells is mediated via the binding of the viral envelope protein, gp120, to the cell surface receptor CD4. This interaction leads to conformational rearrangements in gp120 forming or revealing CD4 induced (CD4i) epitopes which are critical for the subsequent recognition of the co-receptor required for viral entry. The CD4-bound state of gp120 has been considered a potential immunogen for HIV-1 vaccine development. Here we report on an alternative means to induce gp120 into the CD4i conformation.Results: Combinatorial phage display peptide libraries were screened against HIV-1 gp120 and short (14aa) peptides were selected that bind the viral envelope and allosterically induce the CD4i conformation. The lead peptide was subsequently systematically optimized for higher affinity as well as more efficient inductive activity. The peptide:gp120 complex was scrutinized with a panel of neutralizing anti-gp120 monoclonal antibodies and CD4 itself, illustrating that peptide binding does not interfere with or obscure the CD4 binding site.Conclusions: Two surfaces of gp120 are considered targets for the development of cross neutralizing antibodies against HIV-1; the CD4 binding site and CD4i epitopes. By implementing novel peptides that allosterically induce the CD4i epitopes we have generated a viral envelope that presents both of these surfaces simultaneously.",
keywords = "CD4i, HIV-1, Peptide, Phage display, Vaccine, gp120",
author = "Anna Roitburd-Berman and Gal Dela and Gilad Kaplan and Lewis, {George K.} and Gershoni, {Jonathan M.}",
note = "Funding Information: This research was supported by grants from the Israel Science Foundation (JMG), the Frankel Foundation (JMG), generous support of Peter Kraus (JMG), and the Bill and Melinda Gates Foundation (GKL). JMG is the incumbent of the David Furman Chair of Immunobiology in Cancer. ARB received the Dan David Doctoral Fellowship. ARB and GK are the recipients of the Jakov, Miriana, and Jorge Saia Doctoral Fellowship. We would like to acknowledge Michel Nussenzweig, Yongjun Guan, Christopher Broder, Gerald Quinnan and James Robinson for their kind provision of antibodies and envelope proteins. We thank Hanna Bj{\"o}rkelund, Karl Andersson (Ridgeview Instruments AB Uppsala, Sweden) and Susana Geifman Shochat for their critical comments and assistance in the Biacore analyses and Arie Ryvkin for his generous assistance in conducting the Biacore analyses.",
year = "2013",
month = dec,
day = "5",
doi = "10.1186/1742-4690-10-147",
language = "אנגלית",
volume = "10",
journal = "Retrovirology",
issn = "1742-4690",
publisher = "BioMed Central Ltd.",
number = "1",
}