HIV-1 rev antisense phosphorothioate oligonucleotide binding to human mononuclear cells is cell type specific and inducible.
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.
Pirruccello
S J
SJ
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198.
Perry
G A
GA
Bock
P J
PJ
Lang
M S
MS
Noel
S M
SM
Zon
G
G
Iversen
P L
PL
D001483:Base Sequence; D005069:Evaluation Studies as Topic; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000378:metabolism*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000097:blood*; D013873:Thionucleotides / Q000097:blood*
D016376:Oligonucleotides, Antisense; D013873:Thionucleotides