Histone deacetylase inhibitor FR901228 enhances adenovirus infection of hematopoietic cells.
Histone deacetylase inhibitor FR901228 enhances adenovirus infection of hematopoietic cells.
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组蛋白脱乙酰酶抑制剂 FR901228 增强造血细胞的腺病毒感染。
DOI：
10.1182/blood.v99.6.2248
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发表时间：
2002
期刊：
影响因子：
20.3
通讯作者：
M. Goldsmith
中科院分区：
文献类型：
--
作者：
M. Kitazono;V. Rao;R. Robey;T. Aikou;S. Bates;T. Fojo;M. Goldsmith
造血细胞的腺病毒感染通常需要较高的病毒浓度和较长的孵育时间才能获得中等水平的感染，因为这些细胞的柯萨奇病毒和腺病毒受体(CAR)和α(V)整合素水平较低。研究了组蛋白脱乙酰酶抑制剂FR901228对K562细胞、粒细胞集落刺激因子动员的外周血单核细胞(PBMC)和CD34+外周血干细胞(PBSCs)的作用。FR901228增加CAR和α(V)整合素RNA水平和组蛋白H3乙酰化。在腺病毒感染前进行FR901228治疗与表达β-半乳糖苷酶的腺病毒载体的转基因表达至少增加10倍有关。腺病毒感染60分钟后，来自7个不同供者的PBMC或CD34+PBSC中80%以上的PBMC或CD34+PBSCs呈β-半乳糖苷酶阳性。在接受FR901228治疗的患者的PBMC中，观察到CAR、α(V)整合素和乙酰化组蛋白H3水平升高。这些研究表明，FR901228可以提高腺病毒感染造血细胞的效率。
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.
使用常规载体和 RGD 腺病毒载体选择性转导小鼠骨髓单核细胞白血病细胞 (WEHI-3B)。
DOI：
10.1006/mthe.2000.0221
发表时间：
2001
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
García-Castro,J;Segovia,JC;García-Sánchez,F;Lillo,R;Gómez-Navarro,J;Curiel,DT;Bueren,JA
通讯作者：
Bueren,JA
影响因子：
20.3
作者：
Frey, BM;Hackett, NR;Rafii, S
通讯作者：
Rafii, S