Minimal sequence requirements for synthetic peptides derived from the V3 loop of the human immunodeficiency virus type 1 (HIV-1) to enhance HIV-1 binding to cells and infection

C. Zanotto, F. Calderazzo, M. Dettin, C. Di Bello, M. Autiero, J. Guardiola, L. Chieco-Bianchi, A. De Rossi

Research output: Contribution to journalArticlepeer-review

Abstract

We previously demonstrated that a 23-mer peptide (DB3) derived from the V3 loop of the surface glycoprotein of HIV-1 MN strain was able to bind to soluble CD4 and enhance HIV-1 infection. The mechanism and structural features required for these biological activities were studied by using shortened DB3 derivatives and DB3 analogs carrying single amino acid substitutions. We found that peptides in which the aromatic amino acid in position 15 or 16 had been replaced by an uncharged hydrophobic residue (DB3-I15 and DB3-I16), analogs in which positively charged amino acids were replaced by corresponding D-enantiomers, and shortened DB3-derivatives lost both enhancing activity and ability to bind to soluble CD4. Other peptide variants in which a positively charged amino acid was replaced by asparagine at positions 3 (DB3-N3), 6 (DB3-N6), and 19 (DB3-N19), respectively, retained both enhancing and binding activities, although with different efficiencies. The CD4 binder peptides DB3 and DB3-N19, but none of the CD4 nonbinder peptides, enhanced CD4 expression on peptide-treated cells as well as gp120 binding to both CD4+ cells and soluble CD4. These findings strongly suggest that the peptide/CD4 interaction induced an increase in both CD4 expression and CD4/gp120 binding affinity, which in turn mediated the enhancement of viral infection. A model of the structural conformation of DB3 peptide required for its biological activities is discussed.

Original languageEnglish
Pages (from-to)807-816
Number of pages10
JournalVirology
Volume206
Issue number2
DOIs
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Minimal sequence requirements for synthetic peptides derived from the V3 loop of the human immunodeficiency virus type 1 (HIV-1) to enhance HIV-1 binding to cells and infection'. Together they form a unique fingerprint.

Cite this