Mutant TAR virus and transdominant tat mutants as pharmacological agents

摘要

Transdominant HIV tat substitution and truncated gene mutants of 72 amino acid residues or less are disclosed. The mutated genes encode mutant Tat proteins which are capable of inhibiting the expression of the HIV-1 virus in the presence of an equimolar concentration of the wild type Tat protein in vitro. Therapeutic agents which include fused protein forms of the mutant proteins are also disclosed, as well as methods of preparing and using the therapeutic agents in the treatment of HIV infection and HIV-related injections in an animal. Recombinant vectors which express the mutant HIV Tat proteins described are also disclosed, as well as cell lines which product high yields of the mutant HIV. Also provided are cell lines that express enhanced levels of TAR mutant viruses relative to other TAR mutant infected cell lines. Levels of production are enhanced by the use of cell lines that express a transactivator protein, such as adenovirus transactivator EIA and/or EIB protein. Methods of preparing these cell lines, as well as vaccines from virus produced by these cell lines, are also disclosed.