AMPHOTROPIC OR GIBBON APE LEUKEMIA-VIRUS (GALV) RETROVIRUS BINDING AND TRANSDUCTION CORRELATES WITH THE LEVEL OF RECEPTOR MESSENGER-RNA IN HUMAN HEMATOPOIETIC-CELL LINES

The low level of amphotropic retrovirus mediated gene transfer into hu man hematopoietic stem cells (HSC) has been an impediment to gene ther apy for hematopoietic diseases (1), We have previously shown that mous e and human HSC have low levels of the mRNA encoding PiT-2, the amphot ropic 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 leve l of PiT-2 and PiT-1, the Gibbon Ape Leukemia Virus receptor (GaLV), i n 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 retro virus binding and transduction with the appropriate (amphotropic or Ga LV) 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 Inte rleukin-1 alpha. The increase in the level of PiT-2 and PiT-1 mRNA cor related with increased transduction with both amphotropic and GaLV ret roviral vectors. We conclude that the improved transduction was a dire ct effect of the increased levels of receptor mRNA and unrelated to ch anges in the cell cycle status.