In vitro inhibition of R5 HIV-1 infectivity by X4 V3-derived synthetic peptides.
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.
Baritaki
Stavroula
S
Department of Immunology and Applied Biochemistry, IMBB, FORTH, Vassilika Vouton, P.O. Box 1527, GR 711 10 Heraklion, Crete, Greece.
Dittmar
Matthias T
MT
Spandidos
Demetrios A
DA
Krambovitis
Elias
E
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*
D017077:Culture Media, Conditioned; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments