Institute of Tropical Medicine Antwerp
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In vitro activity of candidate microbicides against cell-associated HIV

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dc.contributor.author Selhorst, P.
dc.contributor.author Grupping, K.
dc.contributor.author Bourlet, T.
dc.contributor.author Delezay, O.
dc.contributor.author Ariën, K. K.
dc.contributor.author Vanham, G.
dc.date.accessioned 2012-02-29T11:42:40Z
dc.date.available 2012-02-29T11:42:40Z
dc.date.issued 2012
dc.identifier.issn 0066-4804
dc.identifier.doi http://dx.doi.org/10.1128/AAC.05801-11
dc.identifier.other ITG-B1B
dc.identifier.other ITG-B2B
dc.identifier.other ITG-B5A
dc.identifier.other ITG-BLA
dc.identifier.other DBM
dc.identifier.other U-VIROL
dc.identifier.other JIF
dc.identifier.other DOI
dc.identifier.other UPD43
dc.identifier.uri http://hdl.handle.net/10390/6827
dc.description.abstract Most research on HIV transmission and microbicides focuses on the inhibition of cell-free virus (CFV) present in genital secretions. However, an effective microbicide should also block the transmission of cell-associated virus (CAV) originating from seminal T-cells and macrophages. Because inhibition of CAV remains controversial, especially for viral entry inhibitors, we developed a novel in vitro assay to evaluate the activity of different classes of candidate microbicides against cell-free HIV and HIV-infected leucocytes (i.e, resting PBMC, activated PBMC and monocyte-derived macrophages). The assay is based on two CD4+ CXCR4+ T-cell lines (R5MaRBLE and X4MaRBLE) that both contain a firefly luciferase reporter gene but differ in the expression of the CCR5 co-receptor. Consequently, the quantification of luciferase activity and Gag p24 concentration in co-cultures of R5-tropic HIV-infected leucocytes with each cell line separately allowed to discriminate between the infection of the cell-lines (i.e., target cells), the ongoing infection in the HIV-infected leucocytes (i.e., effector cells), and the total infection of the co-culture (i.e., effector + target cells). All fourteen antiretrovirals tested, were able to block target cell infection by all three sources of CAV, although a small decrease in activity (2 to 18-fold) was observed for all entry inhibitors. On the other hand, the production of Gag p24 by the infected effector cells could only be blocked by protease inhibitors. Overall, these results show that entry and protease inhibitors are eligible drug classes for inclusion in future combination microbicides. en
dc.language English en
dc.subject Viral diseases en
dc.subject HIV en
dc.subject AIDS en
dc.subject Prevention en
dc.subject Development en
dc.subject Microbicides en
dc.subject Transmission interruption en
dc.subject Macrophages en
dc.subject T cells en
dc.subject In vitro en
dc.subject Assays en
dc.subject Leukocytes en
dc.subject Luciferase en
dc.subject Gag en
dc.subject P24 en
dc.subject Entry inhibitors en
dc.subject Protease inhibitors en
dc.subject Non-nucleoside en
dc.subject Reverse transcriptase inhibitors en
dc.subject Integrase inhibitors en
dc.title In vitro activity of candidate microbicides against cell-associated HIV en
dc.type Article en
dc.citation.issue 2 en
dc.citation.jtitle Antimicrobial Agents and Chemotherapy en
dc.citation.volume 56 en
dc.citation.pages 805-815 en
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/22083472
dc.citation.jabbreviation Antimicrob Agents Chemother en


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