Histone deacetylase inhibitor FR901228 enhances adenovirus infection of hematopoietic cells.
Adenovirus infection of hematopoietic cells frequently requires high virus concentrations and long incubation times to obtain moderate infection levels because these cells have low levels of Coxsackie and adenovirus receptor (CAR) and alpha(v) integrin. The effect of treatment with FR901228 (depsipeptide), a histone deacetylase inhibitor in phase 2 clinical trials, was studied in K562 cells, granulocyte-colony-stimulating factor-mobilized peripheral blood mononuclear cells (PBMCs), and CD34+ peripheral blood stem cells (PBSCs). FR901228 increased CAR and alpha(v) integrin RNA levels and histone H3 acetylation. FR901228 treatment before adenovirus infection was associated with at least a 10-fold increase in transgene expression from a beta-galactosidase-expressing adenoviral vector. More than 80% of the PBMCs or CD34+ PBSCs from 7 different donors were beta-galactosidase-positive after adenovirus infection with a multiplicity of infection of 10 for 60 minutes. Increased CAR, alpha(v) integrin, and acetylated histone H3 levels were observed in PBMCs from a patient treated with FR901228. These studies suggest that FR901228 can increase the efficiency of adenoviral infection in hematopoietic cells.
Kitazono
Masaki
M
Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg 10, Rm 12C103, 9000 Rockville Pike, Bethesda, MD 20892-1910, USA. tfojo@helix.nih.gov
Rao
Vemulkonda Koneti
VK
Robey
Rob
R
Aikou
Takashi
T
Bates
Susan
S
Fojo
Tito
T
Goldsmith
Merrill E
ME
D000256:Adenoviridae / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D015703:Antigens, CD / Q000097:blood / Q000187:drug effects; D018952:Antigens, CD34 / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000097:blood / Q000187:drug effects; D047630:Depsipeptides; D004341:Drug Evaluation; D005136:Eye Proteins; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods* / Q000592:standards; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D051597:Hippocalcin; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D039564:Integrin alphaV; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000637:transplantation; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; D010456:Peptides, Cyclic; D051603:Recoverin; D014161:Transduction, Genetic / Q000379:methods; D019076:Transgenes
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D018952:Antigens, CD34; D002135:Calcium-Binding Proteins; D047630:Depsipeptides; D005136:Eye Proteins; D056572:Histone Deacetylase Inhibitors; D039564:Integrin alphaV; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; D010456:Peptides, Cyclic; C496731:RCVRN protein, human; D051603:Recoverin; D051597:Hippocalcin; C087123:romidepsin