Unique Identifier : AIDSLINE MED/99291790
The scaffold attachment region of the human interferon beta gene
(IFN-SAR) inserted into a retroviral vector improved transgene
expression in human primary CD4+ and CD8+ T cells, and in primary
monocytemacrophages. In T cells, expression of the Maloney murine
leukemia virus (Mo-MuLV)-based retroviral vectors was high in activated
cells but low in resting cells. Addition of the IFN-SAR sequence
enhanced vector expression 2- to 10-fold, and the effect was
particularly pronounced in resting T cells. In CD33+CD14+CD4+
monocyte-macrophages derived from transduced hematopoietic
stem/progenitor cells (HSPCs) in vitro, the IFN-SAR enhanced vector
expression three- to sixfold. We have used the IFN-SAR-containing
vectors to express the RevM10 gene, a trans-dominant mutant of the human
immunodeficiency virus type 1 (HIV-1) rev gene. Compared with a standard
retroviral vector, the IFN-SAR-containing vector was significantly (p <
0.01) more potent at inhibiting HIV-1 replication in infected CD4+
peripheral blood lymphocytes. In monocytes, however, addition of the
IFN-SAR did not significantly improve antiviral efficacy. To