OBJECTIVE: To create altered HIV-1 proviruses, containing foreign genes, capable of autonomous replication with either a transdominant inhibitory phenotype or an attenuated phenotype for pathogenicity. METHODS: Four HIV-1 proviruses separately containing a PKR gene, an HSV-1 thymidine kinase gene, an HTLV-I Tax gene, and a ribozyme gene were created. These proviruses were tested in continuous T-lymphocyte cultures either alone or in co-cultivation with wildtype HIV-1 to assay for attenuated pathogenicity versus transdominant inhibitory properties. RESULTS: We have found that proviruses containing PKR, HSV tk, and ribozyme have capacities to be transdominant inhibitors of wildtype HIV-1. An altered HIV-1 containing HTLV-I Tax showed highly reduced pathogenicity in lymphocyte cultures. DISCUSSION: Attenuated HIVs are potentially useful vaccine candidates. Transdominant HIVs that in themselves have been constructed to be attenuated are useful for therapeutic considerations.

Cells, Cultured *Gene Therapy Genes, pX Genes, Viral/GENETICS Human HIV Infections/THERAPY HIV-1/*GENETICS/*PATHOGENICITY HTLV-I/GENETICS Protein-Serine-Threonine Kinases/GENETICS Proviruses/*GENETICS T-Lymphocytes/MICROBIOLOGY Thymidine Kinase/GENETICS ABSTRACT

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