Cellulose acetate 1,2-benzenedicarboxylate inhibits infection by cell-free and cell-associated primary HIV-1 isolates

Abstract

Cellulose acetate 1,2-benzenedicarboxylate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was previously shown to have potent inhibitory activity against infection by human immunodeficiency virus type 1 (HIV-1) T cell line-adapted (TCLA) strains. In the present study, we determined the inhibitory activity of CAP against infection by cell-free and cell-associated primary HIV-1 isolates with distinct genotypes and biotypes in cervical explants, peripheral blood mononuclear cells (PBMCs), monocytederived macrophages (MDMs), and CEMx174 5.25M7 cells. CAP blocked infection by cell-free and cell-associated HIV-1 in cervical explants. It inhibited infection by cell-free primary HIV-1 isolates (clades A to G and group O) in PBMCs, MDMs, and CEMx174 5.25M7 cells and blocked transmissions of the cell-associated primary HIV-1 isolates from dendritic cells (DCs) to PBMCs, from MDMs to PBMCs, and from PBMCs to CEMx174 5.25M7 cells. The inhibitory activity of CAP on infection by the cell-free and cell-associated primary HIV-1 isolates is independent of viral subtypes and coreceptor usage. These data suggest that CAP is a good microbicide candidate that can be further developed for preventing sexual transmission of HIV-1.

FIG. 1

Effects of CAP on cell-free and cell-associated HIV-1 infection of cervical explants. For testing cell-free virus, explants were exposed to HIV-1_BaL diluted in culture medium or in 25% semen in the absence or presence of CAP (1 mg/ml). After extensive washes, explants were cultured for 10 days before measuring p24 antigen. For testing cell-associated virus, explants were exposed to HIV-1_BaL-infected PBMCs in the absence or presence of CAP. After extensive washes, explants were cultured for 10 days, followed by measuring p24 antigen production. Data were obtained from three independent experiments using tissue from different donors and are presented as means ± SE.

FIG. 2

CAP-mediated inhibition of infection by primary HIV-1 isolates of MDMs (A), PBMCs (B), and CEMx174 5.25 M7 cells (C). All the samples were tested in triplicate and averages are presented. The subtypes (clades) and biotypes (coreceptor usage) of the virus isolates tested are shown in each panel.

FIG. 3

CAP-mediated inhibition of transmission of primary HIV-1 isolates from DCs to PBMCs (A), from MDMs to PBMCs (B), and from PBMCs to CEMx174 5.25M7 cells (C). All the samples were tested in triplicate and averages are presented. The subtypes (clades) and biotypes (coreceptor usage) of the virus isolates tested are shown in each panel.