Acquired immunodeficiency syndrome is caused by a human immunodeficiency virus (HIV) that infects and destroys helper T- lymphocytes. These experiments are designed to test whether RNA sequences complimentary to portions of the HIV genome (anti-sense RNA) can block HIV replication or gene expression thereby creating T-lymphocytes that are resistant to the cytopathic affects of HIV. We have established a new construction scheme of expression vectors and tested various promoters and vectors systematically. The human B19 parvovirus promoter was shown to be the most potent promoter so far tested in human T-cell lines. Using the high titer retrovirus vectors containing the B19 promoter driven anti-sense transcriptional units, we have succeeded in creating T-cell lines expressing certain HIV anti-sense sequences at high levels. Several clones have been already tested for their ability to withstand infection by the HIV. However, there was no significant difference in the rate of viral replication between these clones and mock-infected T-cells. We are currently tested whether anti- sense sequences of other portions of the HIV genome can inhibit virus replication. We have also designed several new retrovirus vectors to increase the level of expression of anti-sense sequences. If an effective anti-sense expression retrovirus vector is identified in culture system, the vector may be tested in primates.
