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

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2001 Jan 3

PMID 11134311

Citations 42

Authors

K Verhoef

G Marzio

W Hillen

H Bujard

B Berkhout

Affiliations

Soon will be listed here.

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.

Citing Articles

Impact of Nuclear Export Pathway on Cytoplasmic HIV-1 RNA Transport Mechanism and Distribution.

Chen J, Umunnakwe C, Sun D, Nikolaitchik O, Pathak V, Berkhout B mBio. 2020; 11(6).

PMID: 33172997 PMC: 7667035. DOI: 10.1128/mBio.01578-20.

CRISPR-Cas9 Dual-gRNA Attack Causes Mutation, Excision and Inversion of the HIV-1 Proviral DNA.

Binda C, Klaver B, Berkhout B, Das A Viruses. 2020; 12(3).

PMID: 32197474 PMC: 7150824. DOI: 10.3390/v12030330.

Synthetic biology approach for the development of conditionally replicating HIV-1 vaccine.

Wang N, Yuan Z, Niu W, Li Q, Guo J J Chem Technol Biotechnol. 2017; 92(3):455-462.

PMID: 28983143 PMC: 5624719. DOI: 10.1002/jctb.5174.

Controlling Multicycle Replication of Live-Attenuated HIV-1 Using an Unnatural Genetic Switch.

Yuan Z, Wang N, Kang G, Niu W, Li Q, Guo J ACS Synth Biol. 2017; 6(4):721-731.

PMID: 28106981 PMC: 5400733. DOI: 10.1021/acssynbio.6b00373.

Tet-On Systems For Doxycycline-inducible Gene Expression.

Das A, Tenenbaum L, Berkhout B Curr Gene Ther. 2016; 16(3):156-67.

PMID: 27216914 PMC: 5070417. DOI: 10.2174/1566523216666160524144041.

References

Mikaelian I, Sergeant A . A general and fast method to generate multiple site directed mutations. Nucleic Acids Res. 1992; 20(2):376. PMC: 310390. DOI: 10.1093/nar/20.2.376. View

Peden K, Emerman M, Montagnier L . Changes in growth properties on passage in tissue culture of viruses derived from infectious molecular clones of HIV-1LAI, HIV-1MAL, and HIV-1ELI. Virology. 1991; 185(2):661-72. DOI: 10.1016/0042-6822(91)90537-l. View

Gossen M, Bujard H . Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A. 1992; 89(12):5547-51. PMC: 49329. DOI: 10.1073/pnas.89.12.5547. View

Daniel M, Kirchhoff F, Czajak S, Sehgal P, Desrosiers R . Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science. 1992; 258(5090):1938-41. DOI: 10.1126/science.1470917. View

Berkhout B, Klaver B . In vivo selection of randomly mutated retroviral genomes. Nucleic Acids Res. 1993; 21(22):5020-4. PMC: 310612. DOI: 10.1093/nar/21.22.5020. View

Kirchhoff F, Kestler 3rd H, Desrosiers R . Upstream U3 sequences in simian immunodeficiency virus are selectively deleted in vivo in the absence of an intact nef gene. J Virol. 1994; 68(3):2031-7. PMC: 236672. DOI: 10.1128/JVI.68.3.2031-2037.1994. View

Klaver B, Berkhout B . Premature strand transfer by the HIV-1 reverse transcriptase during strong-stop DNA synthesis. Nucleic Acids Res. 1994; 22(2):137-44. PMC: 307763. DOI: 10.1093/nar/22.2.137. View

Klaver B, Berkhout B . Comparison of 5' and 3' long terminal repeat promoter function in human immunodeficiency virus. J Virol. 1994; 68(6):3830-40. PMC: 236888. DOI: 10.1128/JVI.68.6.3830-3840.1994. View

Klaver B, Berkhout B . Evolution of a disrupted TAR RNA hairpin structure in the HIV-1 virus. EMBO J. 1994; 13(11):2650-9. PMC: 395139. DOI: 10.1002/j.1460-2075.1994.tb06555.x. View

10.

Huang L, Joshi A, Willey R, Orenstein J, Jeang K . Human immunodeficiency viruses regulated by alternative trans-activators: genetic evidence for a novel non-transcriptional function of Tat in virion infectivity. EMBO J. 1994; 13(12):2886-96. PMC: 395170. DOI: 10.1002/j.1460-2075.1994.tb06583.x. View

11.

Ilyinskii P, Daniel M, Simon M, Lackner A, Desrosiers R . The role of upstream U3 sequences in the pathogenesis of simian immunodeficiency virus-induced AIDS in rhesus monkeys. J Virol. 1994; 68(9):5933-44. PMC: 236999. DOI: 10.1128/JVI.68.9.5933-5944.1994. View

12.

Lohman B, McChesney M, Miller C, McGowan E, Joye S, Van Rompay K . A partially attenuated simian immunodeficiency virus induces host immunity that correlates with resistance to pathogenic virus challenge. J Virol. 1994; 68(11):7021-9. PMC: 237139. DOI: 10.1128/JVI.68.11.7021-7029.1994. View

13.

Kirchhoff F, Greenough T, Brettler D, Sullivan J, Desrosiers R . Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N Engl J Med. 1995; 332(4):228-32. DOI: 10.1056/NEJM199501263320405. View

14.

Das A, Klaver B, Berkhout B . Reduced replication of human immunodeficiency virus type 1 mutants that use reverse transcription primers other than the natural tRNA(3Lys). J Virol. 1995; 69(5):3090-7. PMC: 189010. DOI: 10.1128/JVI.69.5.3090-3097.1995. View

15.

Almond N, Kent K, Cranage M, Rud E, Clarke B, Stott E . Protection by attenuated simian immunodeficiency virus in macaques against challenge with virus-infected cells. Lancet. 1995; 345(8961):1342-4. DOI: 10.1016/s0140-6736(95)92540-6. View

16.

Howe J, Skryabin B, Belcher S, Zerillo C, Schmauss C . The responsiveness of a tetracycline-sensitive expression system differs in different cell lines. J Biol Chem. 1995; 270(23):14168-74. DOI: 10.1074/jbc.270.23.14168. View

17.

Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H . Transcriptional activation by tetracyclines in mammalian cells. Science. 1995; 268(5218):1766-9. DOI: 10.1126/science.7792603. View

18.

Berkhout B, van Wamel J, Klaver B . Requirements for DNA strand transfer during reverse transcription in mutant HIV-1 virions. J Mol Biol. 1995; 252(1):59-69. DOI: 10.1006/jmbi.1994.0475. View

19.

Deacon N, Tsykin A, Solomon A, Smith K, Hooker D, McPhee D . Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science. 1995; 270(5238):988-91. DOI: 10.1126/science.270.5238.988. View

20.

Van Rompay K, Spinner A, Otsyula M, McChesney M, Marthas M . Attenuated retrovirus vaccines and AIDS. Science. 1995; 270(5239):1218-9; author reply 1220-2. View