EXPRESSION OF THE ENDOGENOUS RETROVIRUS ERV3 (HERV-R) DURING INDUCED MONOCYTIC DIFFERENTIATION IN THE U-937 CELL-LINE

ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm of chromosome 7. LTR-env-gene-spliced mRNA of 9 and 3.5 Kb i s widely expressed in human tissues and cells, but gag-pol mRNA has no t been found. Further, the env gp70 gene contains an open reading fram e throughout its length and its expression has recently been detected as a full-length protein. The highest expression of ERV3 detected so f ar is in placenta and the lowest in cytotrophoblasts and choriocarcino ma cell lines. In this report we have studied ERV3 mRNA and protein ex pression in the human monoblastic cell line U-937 during differentiati on into monocytes/macrophages. Differentiation of U-937 cells was indu ced by 1,25a-dihydroxyvitamin D-3 (vitD(3)), retinoic acid (RA), gamma interferon (IFN-gamma) and phorbol-myristate-acetate (PMA-TPA). The e xpression of ERV3 env mRNA was found to be differentiation-associated, with high expression detected in the late stages of monocytic develop ment. Using TPA, the expression of ERV3 env was detected as 9- and 3.5 -kb transcripts by Northern blotting, as mRNA by in situ hybridization and as a cytoplasmic 65-kDa protein by immunofluorescence and Western blots. Low levels of basal expression were found, with up-regulation of both message and protein at 24 to 48 hr after addition of TPA. Indu ction with vitD(3), IFN-gamma and RA produced higher levels of mRNA at earlier time points. It is concluded that the U-937 cell line represe nts an excellent model system for further studies to study the relatio nship between ERV3 expression and cellular differentiation. (C) 1996 W iley-Liss, Inc.