期刊
JOURNAL OF VIROLOGY
卷 75, 期 2, 页码 979-987出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.75.2.979-987.2001
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Live-attenuated human immunodeficiency virus type 1 (HIV-1) variants have shown great promise as AIDS vaccines, but continued replication can lead to the selection of faster-replicating variants that are pathogenic. We therefore designed HIV-1 genomes that replicate exclusively upon addition of the nontoxic effector doxycycline (dox), This was achieved by replacement of the viral TAR-Tat system for transcriptional activation by the Echerichia coli-derived Tet system for inducible gene expression. These designer HIV-rtTA viruses replicate in a strictly dox-dependent manner both in a T-cell line and in primary blood cells, and the rate of replication can be fine-tuned by simple variation of the dox concentration. These HIV-rtTA viruses provide a tool to perform genetics, e.g., selection and optimization experiments, with the E. coli-derived Tet reagents in a eukaryotic background. Furthermore, such viruses may represent improved vaccine candidates because their replication can be turned on and off at will.
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