Histone deacetylase inhibitor FR901228 enhances adenovirus infection of hematopoietic cells

• Published in: Blood Vol. 99; no. 6; pp. 2248 - 2251
• Main Authors: Kitazono, Masaki, Rao, Vemulkonda Koneti, Robey, Rob, Aikou, Takashi, Bates, Susan, Fojo, Tito, Goldsmith, Merrill E.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-03-2002; The Americain Society of Hematology
• Subjects: Adenoviridae - genetics; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacology; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacology; Antigens, CD - blood; Antigens, CD - drug effects; Antigens, CD34 - metabolism; Antineoplastic agents; Biological and medical sciences; Biotechnology; Calcium-Binding Proteins - blood; Calcium-Binding Proteins - drug effects; Chemotherapy; Depsipeptides; Drug Evaluation; Eye Proteins; Fundamental and applied biological sciences. Psychology; Gene therapy; Genes, Reporter; Genetic Therapy - methods; Genetic Therapy - standards; Health. Pharmaceutical industry; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells - metabolism; Hippocalcin; Histone Deacetylase Inhibitors; Humans; Industrial applications and implications. Economical aspects; Integrin alphaV; K562 Cells; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - transplantation; Lipoproteins; Medical sciences; Nerve Tissue Proteins; Peptides, Cyclic; Pharmacology. Drug treatments; Recoverin; Transduction, Genetic - methods; Transgenes; Adenoviridae; Hematopoietic cell; Enzyme inhibitor; In vitro; Virus; Infection; Chemotherapy; Treatment; Depsipeptide; Established cell line; Feasibility; Combined treatment; Gene therapy; Vector; Virus penetration
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V99.6.2248

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 αv 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 αvintegrin 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 β-galactosidase–expressing adenoviral vector. More than 80% of the PBMCs or CD34+ PBSCs from 7 different donors were β-galactosidase–positive after adenovirus infection with a multiplicity of infection of 10 for 60 minutes. Increased CAR, αv 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.