Peptide-derivatized SB105-A10 dendrimer inhibits the infectivity of R5 and X4 HIV-1 strains in primary PBMCs and cervicovaginal histocultures

PLoS One. 2013 Oct 7;8(10):e76482. doi: 10.1371/journal.pone.0076482. eCollection 2013.

Abstract

Peptide dendrimers are a class of molecules that exhibit a large array of biological effects including antiviral activity. In this report, we analyzed the antiviral activity of the peptide-derivatized SB105-A10 dendrimer, which is a tetra-branched dendrimer synthetized on a lysine core, in activated peripheral blood mononuclear cells (PBMCs) that were challenged with reference and wild-type human immunodeficiency virus type 1 (HIV-1) strains. SB105-A10 inhibited infections by HIV-1 X4 and R5 strains, interfering with the early phases of the viral replication cycle. SB105-A10 targets heparan sulfate proteoglycans (HSPGs) and, importantly, the surface plasmon resonance (SPR) assay revealed that SB105-A10 strongly binds gp41 and gp120, most likely preventing HIV-1 attachment/entry through multiple mechanisms. Interestingly, the antiviral activity of SB105-A10 was also detectable in an organ-like structure of human cervicovaginal tissue, in which SB105-A10 inhibited the HIV-1ada R5 strain infection without altering the tissue viability. These results demonstrated the strong antiviral activity of SB105-A10 and suggest a potential microbicide use of this dendrimer to prevent the heterosexual transmission of HIV-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Cervix Uteri / drug effects*
  • Cervix Uteri / virology
  • Dendrimers / chemistry
  • Dendrimers / metabolism
  • Dendrimers / pharmacology*
  • Female
  • Flow Cytometry
  • HIV Envelope Protein gp120 / metabolism
  • HIV Envelope Protein gp41 / metabolism
  • HIV Infections / virology
  • HIV-1 / classification
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Host-Pathogen Interactions / drug effects
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / virology
  • Molecular Structure
  • Peptides / chemistry
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Protein Binding
  • Species Specificity
  • Tissue Culture Techniques
  • Vagina / drug effects*
  • Vagina / virology
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Dendrimers
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Peptides
  • SB105-A10
  • gp41 protein, Human immunodeficiency virus 1

Grants and funding

This work was supported by Italian Ministry of Health (AIDS project), University of Bologna (selected topics) and MURST 60%. The authors acknowledge a grant for the Lagrange Project - Crt Foundation. This study was partially funded by Spider Biotech grant to DG for the purchase of reagents. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.