HIV-1 rev Antisense Phosphorothioate Oligonucleotide Binding to Human Mononuclear Cells Is Cell Type Specific and Inducible

Abstract

A fluorescein-conjugated, antisense phosphorothioate oligonucleotide with specificity for HIV-1 rev sequence (FAM-anti-rev) was investigated for its ability to bind to specific subsets of human peripheral blood mononuclear cells. Oligonucleotide binding by CD4⁺ and CD8+ T cells, B cells, and monocytes isolated from 15 normal and 15 HIV-infected individuals was evaluated on both nonstimulated mononuclear cells and after 24-hr activation with phytohemagglutinin (PHA). In both normals and HIV-infected individuals, we found a significantly higher percentage of monocytes and B cells binding oligonucleotide in comparison to T cells. Oligonucleotide binding by both T cells and B cells was enhanced by 24-hr PHA stimulation while monocyte uptake was unchanged. In comparison to normal controls, HIV-1-infected patients showed slightly higher percentages of both unstimulated and PHA activated CD4⁺, CD8⁺, and CD25⁺ T cells binding oligonucleotide. The propensity for a high percentage of monocytes, which may act as an HIV-1 reservoir, to bind the anti-rev oligonucleotide and the enhanced binding by T cells in the HIV-1-infected patient samples provides some optimism for potential in vivo therapy of HIV-1 infection using antisense oligonucleotides.