Amphotropic or Gibbon ape leukemia virus (GaLV) retrovirus binding and transduction correlates with the level of receptor mRNA in human hematopoietic cell lines

被引:43
|
作者
Sabatino, DE
Do, BKQ
Pyle, LC
Seidel, NE
Girard, LJ
Spratt, SK
Orlic, D
Bodine, DM
机构
[1] Natl Human Genome Res Inst, Lab Gene Transfer, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA
[2] Somatix Therapy Corp, Alameda, CA USA
基金
美国国家卫生研究院;
关键词
HL60; cells; PMA; Interleukin-1; alpha; gene expression;
D O I
10.1006/bcmd.1997.0161
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The low level of amphotropic retrovirus mediated gene transfer into human hematopoietic stem cells (HSC) has been an impediment to gene therapy for hematopoietic diseases (1), We have previously shown that mouse and human HSC have low levels of the mRNA encoding PiT-2, the amphotropic retrovirus receptor, We hypothesized that the low level of PiT-2 mRNA was responsible for the low frequency of transduction of HSC by amphotropic retroviral vectors (2), In this study we compared the level of PiT-2 and PiT-1, the Gibbon Ape Leukemia Virus receptor (GaLV), in 5 human tissue culture cell lines, PiT-2 and PiT-1 mRNA levels were highest in K562 cells and lowest in HL60 cells. In hematopoietic cell lines, the level of PiT-2 or PiT-1 mRNA correlated directly with retrovirus binding and transduction with the appropriate (amphotropic or GaLV) retrovirus vector, The level of expression of PiT-2 and PiT-1 mRNA could be increased by treatment of HL60 cells with either PMA or Interleukin-1 alpha. The increase in the level of PiT-2 and PiT-1 mRNA correlated with increased transduction with both amphotropic and GaLV retroviral vectors. We conclude that the improved transduction was a direct effect of the increased levels of receptor mRNA and unrelated to changes in the cell cycle status.
引用
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页码:422 / 433
页数:12
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