DOI: 10.1128/jvi.75.2.979-987.2001. Strict Control of Human Immunodeficiency Virus Type 1 Replication by a Genetic Switch: Tet for Tat

Strict Control of Human Immunodeficiency Virus Type 1 Replication by a Genetic Switch: Tet for Tat

10.1128/jvi.75.2.979-987.2001

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT 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 Escherichia 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.

Bibliography

Verhoef, K., Marzio, G., Hillen, W., Bujard, H., & Berkhout, B. (2001). Strict Control of Human Immunodeficiency Virus Type 1 Replication by a Genetic Switch: Tet for Tat. Journal of Virology, 75(2), 979â987.

Authors 5

Koen Verhoef (first)
Giuseppe Marzio (additional)
Wolfgang Hillen (additional)
Hermann Bujard (additional)
Ben Berkhout (additional)

References 55 Referenced 75

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Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 6:06 a.m.)
Deposited	3 years, 5 months ago (March 5, 2022, 1:33 a.m.)
Indexed	4 months, 3 weeks ago (April 8, 2025, 9:57 p.m.)
Issued	24 years, 7 months ago (Jan. 15, 2001)
Published	24 years, 7 months ago (Jan. 15, 2001)
Published Print	24 years, 7 months ago (Jan. 15, 2001)

Funders 0

None

BibTeX

@article{Verhoef_2001, title={Strict Control of Human Immunodeficiency Virus Type 1 Replication by a Genetic Switch: Tet for Tat}, volume={75}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.75.2.979-987.2001}, DOI={10.1128/jvi.75.2.979-987.2001}, number={2}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Verhoef, Koen and Marzio, Giuseppe and Hillen, Wolfgang and Bujard, Hermann and Berkhout, Ben}, year={2001}, month=jan, pages={979–987} }

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