Enhancement and Induction of HIV‐1 Infection through an Assembled Peptide Derived from the CD4 Binding Site of gp120 |
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| Authors: | Dr Andrea Groß Katja Rödel Barbara Kneidl Norbert Donhauser Marek Mössl Edina Lump Prof Dr Jan Münch Prof Dr Barbara Schmidt Prof Dr Jutta Eichler |
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| Affiliation: | 1. Department of Chemistry and Pharmacy, University of Erlangen–Nurnberg, Schuhstrasse 19, 91052 Erlangen (Germany);2. Institute of Clinical and Molecular Virology, University of Erlangen‐Nurnberg, Schlossgarten 4, 91054 Erlangen (Germany);3. Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081Ulm (Germany);4. Institute of Medical Microbiology and Hygiene, University of Regensburg, Franz‐Josef‐Strau?‐Allee 11, 93053 Regensburg (Germany) |
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| Abstract: | Contact between the human immunodeficiency virus (HIV‐1) and its target cell is initiated by the interaction of viral gp120 with cellular CD4. An assembled peptide (CD4bs‐M) that presents the CD4 binding site of gp120 was previously shown to inhibit the gp120–CD4 interaction. Here, we demonstrate that CD4bs‐M selectively enhances infection of cells with HIV‐1, whereas infection with herpes simplex virus remains largely unaffected. The effects of CD4bs‐M variants containing D ‐amino acids, or prolines at selected positions, point to the importance of side chain orientation and spatial orientation of this fragment. Furthermore, CD4bs‐M was shown to assemble into amyloid‐like fibrils that capture HIV‐1 particles, which likely contributes to the infection‐enhancing effect. Beyond infection enhancement, CD4bs‐M enabled HIV‐1 infection of CD4‐negative cells, suggesting that binding of the peptide to gp120 facilitates interaction of gp120 with coreceptors, which might in turn enhance HIV‐1 entry. |
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| Keywords: | fibrils gp120 HIV‐1 infection enhancement peptides |
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