Short Communication: Inhibition of DC-SIGN-Mediated HIV-1 Infection by Complementary Actions of Dendritic Cell Receptor Antagonists and Env-Targeting Virus Inactivators.

Abstract

The DC-SIGN receptor on human dendritic cells interacts with HIV gp120 to promote both infection of antigen-presenting cells and transinfection of T cells. We hypothesized that in DC-SIGN-expressing cells, both DC-SIGN ligands such as dextrans and gp120 antagonists such as peptide triazoles would inhibit HIV infection with potential complementary antagonist effects. To test this hypothesis, we evaluated the effects of dextran (D66), isomaltooligosaccharides (D06), and several peptide triazoles (HNG156, K13, and UM15) on HIV infection of B-THP-1/DC-SIGN cells. In surface plasmon resonance competition assays, D66 (IC50 = 35.4 μM) and D06 (IC50 = 3.4 mM) prevented binding of soluble DC-SIGN to immobilized mannosylated bovine serum albumin (BSA). An efficacious dose-dependent inhibition of DC-SIGN-mediated HIV infection in both pretreatment and posttreatment settings was observed, as indicated by inhibitory potentials (EC50) [D66 (8 μM), D06 (48 mM), HNG156 (40 μM), UM15 (100 nM), and K13 (25 nM)]. Importantly, both dextrans and peptide triazoles significantly decreased HIV gag RNA levels [D66 (7-fold), D06 (13-fold), HNG156 (7-fold), K-13 (3-fold), and UM15 (6-fold)]. Interestingly, D06 at the highest effective concentration showed a 14-fold decrease of infection, while its combination with 50 μM HNG156 showed a 26-fold decrease. Hence, these compounds can combine to inactivate the viruses and suppress DC-SIGN-mediated virus-cell interaction that as shown earlier leads to dendritic cell HIV infection and transinfection dependent on the DC-SIGN receptor.

• Authors: Sergey Pustylnikov, Rajnish S Dave, Zafar K Khan, Vanessa Porkolab, Adel A Rashad, Matthew Hutchinson, Frank Fieschi, Irwin Chaiken, Pooja Jain
• Journal: AIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 32 Issue 1 Pg. 93-100 (Jan 2016) ISSN: 1931-8405 [Electronic] United States
• PMID: 26383762 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules
• DC-specific ICAM-3 grabbing nonintegrin
• Dextrans
• HIV Envelope Protein gp120
• Lectins, C-Type
• Ligands
• Oligosaccharides
• Peptides
• Receptors, Cell Surface
• Serum Albumin
• Triazoles
• gag Gene Products, Human Immunodeficiency Virus
• mannose-bovine serum albumin conjugate
• Mannose

Topics

• Binding Sites
• Cell Adhesion Molecules (antagonists & inhibitors, genetics, metabolism)
• Cell Line
• Dendritic Cells (drug effects, metabolism, virology)
• Dextrans (metabolism, pharmacology)
• Gene Expression Regulation
• HIV Envelope Protein gp120 (antagonists & inhibitors, genetics, metabolism)
• HIV-1 (drug effects, genetics, metabolism)
• Host-Pathogen Interactions
• Humans
• Lectins, C-Type (antagonists & inhibitors, genetics, metabolism)
• Ligands
• Mannose (antagonists & inhibitors, metabolism)
• Oligosaccharides (metabolism, pharmacology)
• Peptides (metabolism, pharmacology)
• Protein Binding
• Receptors, Cell Surface (antagonists & inhibitors, genetics, metabolism)
• Serum Albumin (antagonists & inhibitors, metabolism)
• Signal Transduction
• Triazoles (metabolism, pharmacology)
• Viral Load (drug effects)
• gag Gene Products, Human Immunodeficiency Virus (antagonists & inhibitors, biosynthesis, genetics)