title: In vitro inhibition of R5 HIV-1 infectivity by X4 V3-derived synthetic peptides.
abstract: The aim of the present study was to investigate the inhibitory effect of synthetic peptides derived from the principle neutralizing domain of the V3 loop of the HIV-1 gp120 in the infectivity rates of HIV-1 variants with different tropism. Assessment of the viral infectivity was determined by detection of soluble HIV p24gag antigen in the culture supernatants of PM-1 T cells and primary macrophages after in vitro infection with the R5, Ba-L and X4, NL4.3 variants in the presence or absence of soluble V3-derived synthetic peptides. Our results showed a clear inhibition of Ba-L infectivity in both the PM-1 T cells and primary macrophages. The degree of inhibition was related to the number of basic amino acids in the peptide. The most effective inhibitory peptide, at a concentration of 50 ng/ml, was the one with the highest cationic potential, achieving over 60% inhibition to the PM-1 T cell line and over 90% to primary macrophages. The same peptides did not affect the NL4.3 infectivity. In addition to our previously reported observations on the electrostatic nature of the V3-CCR5 interaction, we show here that V3-like peptides from the more electropositive X4 variants may be useful as effective antagonists and potential infectivity blockers of the R5 variants.
authors: Department of Immunology and Applied Biochemistry, IMBB, FORTH, Vassilika Vouton, P.O. Box 1527, GR 711 10 Heraklion, Crete, Greece.
authors: Stavroula
authors: S
authors: Baritaki
authors: Matthias T
authors: MT
authors: Dittmar
authors: Demetrios A
authors: DA
authors: Spandidos
authors: Elias
authors: E
authors: Krambovitis
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D014644:Genetic Variation; D016655:HIV Core Protein p24 / Q000032:analysis; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000821:virology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D017077:Culture Media, Conditioned; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments