Carbohydrate-binding agents (CBAs) inhibit HIV-1 infection in human primary monocyte-derived macrophages (MDMs) and efficiently prevent MDM-directed viral capture and subsequent transmission to CD4+ T lymphocytes.
Carbohydrate-binding agents (CBAs) have been proposed as innovative anti-HIV compounds selectively targeting the glycans of the HIV-1 envelope glycoprotein gp120 and preventing DC-SIGN-directed HIV capture by dendritic cells (DCs) and transmission to CD4(+) T-lymphocytes. We now show that CBAs efficiently prevent R5 HIV-1 infection of human primary monocyte-derived macrophage (MDM) cell cultures in the nanomolar range. Both R5 and X4 HIV-1 strains were efficiently captured by the macrophage mannose-binding receptor (MMR) present on MDM. HIV-1 capture by MMR-expressing MDM was inhibited by soluble mannose-binding lectin and MMR antibody. Short pre-exposure of these HIV-1 strains to CBAs is able to prevent virus capture by MDM and subsequent syncytia formation in cocultures of the CBA-exposed HIV-1-captured MDM and uninfected CD4(+) T-lymphocytes. The potential of CBAs to impair MDM in their capacity to capture and to transmit HIV to T-lymphocytes might be an important property to be taken into consideration in the eventual choice to select microbicide candidate drugs for clinical investigation.
Pollicita
M
M
University of Rome, Tor Vergata, Italy.
Schols
D
D
Aquaro
S
S
Peumans
W J
WJ
Van Damme
E J M
EJ
Perno
C F
CF
Balzarini
J
J
D019380:Anti-HIV Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D037121:Plant Lectins / Q000378:metabolism / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D019380:Anti-HIV Agents; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D037121:Plant Lectins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin