title: Enhancement and induction of HIV-1 infection through an assembled peptide derived from the CD4 binding site of gp120.
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.
authors: Department of Chemistry and Pharmacy, University of Erlangen-Nurnberg, Schuhstrasse 19, 91052 Erlangen (Germany).
authors: Andrea
authors: A
authors: Groß
authors: Katja
authors: K
authors: Rödel
authors: Barbara
authors: B
authors: Kneidl
authors: Norbert
authors: N
authors: Donhauser
authors: Marek
authors: M
authors: Mössl
authors: Edina
authors: E
authors: Lump
authors: Jan
authors: J
authors: Münch
authors: Barbara
authors: B
authors: Schmidt
authors: Jutta
authors: J
authors: Eichler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D002522:Chlorocebus aethiops; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity*; D006367:HeLa Cells / Q000821:virology; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D014709:Vero Cells / Q000821:virology
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments
keywords: HIV-1; fibrils; gp120; infection enhancement; peptides