RETROVIRUS VECTOR-TARGETED INDUCIBLE EXPRESSION OF HUMAN INTERFERON-BETA GENE TO B-CELLS

We have introduced the human β-interferon gene with its promoter region into murine B-cell and fibroblast cell lines via a Moloney murine leukemia virus (M-MuLV) vector and have studied the inducible expression of the β-interferon gene as a function of the various retroviral vector designs. By deleting the enhancer within the 3′ viral long terminal repeat (LTR), inserting the human β-interferon gene, and varying placement of the immunoglobulin heavy chain enhancer, we were able to construct vectors which yielded proviruses with various cell type-specific regulation. One of the vectors (pT154) led to a greater than 21-fold increase in β-interferon protein synthesis after viral infection in the two B-cell lines analyzed, while no inducibility was seen in the fibroblast cells. The data show that inducible β-interferon expression within a MuLV vector was highly dependent on the absence of the viral enhancer region in the long terminal repeat and the orientation of the β-interferon gene within the proviral transcriptional unit; the insertion of the immunoglobulin enhancer elevated both constitutive and (or) inducible expression of β-interferon in B-cells but inhibited constitutive expression of this gene in fibroblasts. © 1990.