This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lisziewicz, J. Articles by Peng, B. Search for Related Content PubMed PubMed Citation Articles by Lisziewicz, J. Articles by Peng, B.

 Previous Article  |  Next Article 

J. Virol., 01 1995, 206-212, Vol 69, No. 1
Copyright © 1995, American Society for Microbiology

An autoregulated dual-function antitat gene for human immunodeficiency virus type 1 gene therapy

J Lisziewicz, D Sun, B Trapnell, M Thomson, HK Chang, B Ensoli and B Peng
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland 20892.

One approach to gene therapy for AIDS is to block the replication of human immunodeficiency virus type 1 (HIV-1) by inhibiting that tat gene, whose product activates the expression of all HIV-1 genes. To accomplish this, we constructed an antitat gene expressing an RNA with dual (polymeric TAR and antisense-tat) function in an attempt to both sequester Tat protein and block its translation from mRNA. A minigene consisting of the antitat gene driven by the HIV-1 long terminal repeat was inserted into a double-copy retrovirus vector, such that antitat expression would be upregulated only in HIV-1-infected cells. After transduction of a T-lymphocytic cell line (Molt-3) the antitat gene inhibited HIV-1 replication. This inhibition was inversely correlated with the virus infections dose. Virus replication was also inhibited for 5 months in two different T-cell lines after they had been infected at a high multiplicity of infection, suggesting that the antitat gene may be effective over long periods. Importantly, antitat blocked the replication and the cytopathic effect of HIV-1 in human peripheral blood mononuclear cells and led to as much as 4,000-fold inhibition of the replication of an HIV-1 field isolate as well as HIV-1 prototypes maintained in culture. These results suggest that antitat gene therapy has potential use for blocking HIV-1 replication in infected individuals.