Journal
VIROLOGY
Volume 370, Issue 2, Pages 382-391Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2007.08.033
Keywords
monocyte-derived macrophages (MDMs); carbohydrate-binding agents (CBAs); glycans; HIV-1; envelope glycoprotein gp120; HIV-1 capture; HIV-1 transmission; DC-SIGN; macrophage mannose-binding receptor (MMR)
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Carbohydrate-binding agents (CBAs) have been proposed as innovative anti-HIV compounds selectively targeting the glycans of the HIV-1 envelope glycoprotein gp 120 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. (c) 2007 Elsevier Inc. All rights reserved.
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