Short Communication: Inhibition of DC-SIGN-Mediated HIV-1 Infection by Complementary Actions of Dendritic Cell Receptor Antagonists and Env-Targeting Virus Inactivators
Sergey Pustylnikov, Rajnish S. Dave, Zafar K. Khan, Vanessa Porkolab, Adel A. Rashad, Matthew Hutchinson, Frank Fieschi, Irwin Chaiken and Pooja Jain
AIDS research and human retroviruses, v 32(1), pp 93-100
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 (IC
50
= 35.4 μM) and D06 (IC
50
= 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 (EC
50
) [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.
Short Communication: Inhibition of DC-SIGN-Mediated HIV-1 Infection by Complementary Actions of Dendritic Cell Receptor Antagonists and Env-Targeting Virus Inactivators
Creators
Sergey Pustylnikov - State Research Center of Virology and Biotechnology VECTOR
Rajnish S. Dave - Drexel University
Zafar K. Khan - Drexel University
Vanessa Porkolab - Institut de Biologie Structurale
Adel A. Rashad - Drexel University
Matthew Hutchinson - Drexel University
Frank Fieschi - Institut de Biologie Structurale
Irwin Chaiken - Drexel University
Pooja Jain - Drexel University
Publication Details
AIDS research and human retroviruses, v 32(1), pp 93-100
Publisher
Mary Ann Liebert, Inc
Resource Type
Journal article
Language
English
Academic Unit
Biochemistry and Molecular Biology; Microbiology and Immunology
Web of Science ID
WOS:000367335100013
Scopus ID
2-s2.0-84954121750
Other Identifier
991019167414104721
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