Publication
Title
**In vitro** activities of candidate microbicides against cell-associated HIV
Author
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 activities of different classes of candidate microbicides against cell-free HIV and HIV-infected leukocytes (i.e., resting peripheral blood mononuclear cells [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 coreceptor. Consequently, the quantification of the luciferase activities and the Gag p24 concentrations in cocultures of R5-tropic HIV-infected leukocytes with each cell line separately allowed us to discriminate between the infection of the cell lines (i.e., target cells), the ongoing infection in the HIV-infected leukocytes (i.e., effector cells), and the total infection of the coculture (i.e., effector plus target cells). All 14 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 be blocked only by protease inhibitors. Overall, these results show that entry and protease inhibitors are eligible drug classes for inclusion in future combination microbicides.
Language
English
Source (journal)
Antimicrobial agents and chemotherapy. - Washington, D.C.
Publication
Washington, D.C. : 2012
ISSN
0066-4804
Volume/pages
56:2(2012), p. 805-815
ISI
000299658900028
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 05.03.2012
Last edited 23.06.2017
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