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Science 18 December 1992:
Vol. 258. no. 5090, pp. 1938 - 1941
DOI: 10.1126/science.1470917
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Articles

Science, Vol 258, Issue 5090, 1938-1941
Copyright © 1992 by American Association for the Advancement of Science

articles

Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene

MD Daniel, F Kirchhoff, SC Czajak, PK Sehgal, and RC Desrosiers

New England Regional Primate Research Center, Harvard Medical School, Southborough, MA 01772.

Vaccine protection against the human immunodeficiency virus (HIV) and the related simian immunodeficiency virus (SIV) in animal models is proving to be a difficult task. The difficulty is due in large part to the persistent, unrelenting nature of HIV and SIV infection once infection is initiated. SIV with a constructed deletion in the auxiliary gene nef replicates poorly in rhesus monkeys and appears to be nonpathogenic in this normally susceptible host. Rhesus monkeys vaccinated with live SIV deleted in nef were completely protected against challenge by intravenous inoculation of live, pathogenic SIV. Deletion of nef or of multiple genetic elements from HIV may provide the means for creating a safe, effective, live attenuated vaccine to protect against acquired immunodeficiency syndrome (AIDS).


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Nef interference with HIV-1-specific CTL antiviral activity is epitope specific.
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J. Virol. 79, 12871-12879
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Comparative Immunogenicity of Human Immunodeficiency Virus Particles and Corresponding Polypeptides in a DNA Vaccine.
W. Akahata, Z.-y. Yang, and G. J. Nabel (2005)
J. Virol. 79, 626-631
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Readily acquired secondary infections of human and simian immunodeficiency viruses following single intravenous exposure in non-human primates.
P. t. Haaft, E. J. Verschoor, B. Verstrepen, H. Niphuis, R. Dubbes, W. Koornstra, W. Bogers, B. Rosenwirth, and J. L. Heeney (2004)
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G. A. Mackay, Z. Liu, D. K. Singh, M. S. Smith, S. Mukherjee, D. Sheffer, F. Jia, I. Adany, K. H. Sun, S. Dhillon, et al. (2004)
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J. Virol. 78, 5311-5323
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J. Virol. 78, 4907-4913
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DNA Vaccines against Human Immunodeficiency Virus Type 1 in the Past Decade.
M. Giri, K. E. Ugen, and D. B. Weiner (2004)
Clin. Microbiol. Rev. 17, 370-389
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Control of Simian/Human Immunodeficiency Virus Viremia and Disease Progression after IL-2-Augmented DNA-Modified Vaccinia Virus Ankara Nasal Vaccination in Nonhuman Primates.
F. M. N. Bertley, P. A. Kozlowski, S.-W. Wang, J. Chappelle, J. Patel, O. Sonuyi, G. Mazzara, D. Montefiori, A. Carville, K. G. Mansfield, et al. (2004)
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Early protection against pathogenic virus infection at a mucosal challenge site after vaccination with attenuated simian immunodeficiency virus.
K. Tenner-Racz, C. S. Hennig, K. Uberla, H. Stoiber, R. Ignatius, J. Heeney, R. M. Steinman, and P. Racz (2004)
PNAS 101, 3017-3022
   Abstract »    Full Text »    PDF »
Protection against Mucosal Simian Immunodeficiency Virus SIVmac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting.
L. J. Patterson, N. Malkevitch, D. Venzon, J. Pinczewski, V. R. Gomez-Roman, L. Wang, V. S. Kalyanaraman, P. D. Markham, F. A. Robey, and M. Robert-Guroff (2004)
J. Virol. 78, 2212-2221
   Abstract »    Full Text »    PDF »
Simian Immunodeficiency Virus Promoter Exchange Results in a Highly Attenuated Strain That Protects against Uncloned Challenge Virus.
P. Blancou, N. Chenciner, R. H. T. Fang, V. Monceaux, M.-C. Cumont, D. Guetard, B. Hurtrel, and S. Wain-Hobson (2004)
J. Virol. 78, 1080-1092
   Abstract »    Full Text »    PDF »
High Attenuation and Immunogenicity of a Simian Immunodeficiency Virus Expressing a Proteolysis-resistant Inhibitor of NF-{kappa}B.
I. Quinto, A. Puca, J. Greenhouse, P. Silvera, J. Yalley-Ogunro, M. G. Lewis, C. Palmieri, F. Trimboli, R. Byrum, J. Adelsberger, et al. (2004)
J. Biol. Chem. 279, 1720-1728
   Abstract »    Full Text »    PDF »
Human Immunodeficiency Virus Type 1 Superinfection Was Not Detected following 215 Years of Injection Drug User Exposure.
R. Tsui, B. L. Herring, J. D. Barbour, R. M. Grant, P. Bacchetti, A. Kral, B. R. Edlin, and E. L. Delwart (2004)
J. Virol. 78, 94-103
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A Single Injection of Recombinant Measles Virus Vaccines Expressing Human Immunodeficiency Virus (HIV) Type 1 Clade B Envelope Glycoproteins Induces Neutralizing Antibodies and Cellular Immune Responses to HIV.
C. Lorin, L. Mollet, F. Delebecque, C. Combredet, B. Hurtrel, P. Charneau, M. Brahic, and F. Tangy (2004)
J. Virol. 78, 146-157
   Abstract »    Full Text »    PDF »
Identification of Sequential Viral Escape Mutants Associated with Altered T-Cell Responses in a Human Immunodeficiency Virus Type 1-Infected Individual.
M. J. Geels, M. Cornelissen, H. Schuitemaker, K. Anderson, D. Kwa, J. Maas, J. T. Dekker, E. Baan, F. Zorgdrager, R. van den Burg, et al. (2003)
J. Virol. 77, 12430-12440
   Abstract »    Full Text »    PDF »
Covalently Linked Human Immunodeficiency Virus Type 1 gp120/gp41 Is Stably Anchored in Rhabdovirus Particles and Exposes Critical Neutralizing Epitopes.
P. M. McKenna, R. J. Pomerantz, B. Dietzschold, J. P. McGettigan, and M. J. Schnell (2003)
J. Virol. 77, 12782-12794
   Abstract »    Full Text »    PDF »
AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Protection from an Intraclade Challenge Administered Systemically or Mucosally by an Attenuated Vaccine.
M. Pistello, D. Matteucci, F. Bonci, P. Isola, P. Mazzetti, L. Zaccaro, A. Merico, D. Del Mauro, N. Flynn, and M. Bendinelli (2003)
J. Virol. 77, 10740-10750
   Abstract »    Full Text »    PDF »
Functional Human Immunodeficiency Virus Type 1 (HIV-1) Gag-Pol or HIV-1 Gag-Pol and Env Expressed from a Single Rhabdovirus-Based Vaccine Vector Genome.
J. P. McGettigan, K. Naper, J. Orenstein, M. Koser, P. M. McKenna, and M. J. Schnell (2003)
J. Virol. 77, 10889-10899
   Abstract »    Full Text »    PDF »
Potent, Persistent Induction and Modulation of Cellular Immune Responses in Rhesus Macaques Primed with Ad5hr-Simian Immunodeficiency Virus (SIV) env/rev, gag, and/or nef Vaccines and Boosted with SIV gp120.
L. J. Patterson, N. Malkevitch, J. Pinczewski, D. Venzon, Y. Lou, B. Peng, C. Munch, M. Leonard, E. Richardson, K. Aldrich, et al. (2003)
J. Virol. 77, 8607-8620
   Abstract »    Full Text »    PDF »
DNA vaccination of macaques by a full-genome simian/human immunodeficiency virus type 1 plasmid chimera that produces non-infectious virus particles.
W. Akahata, E. Ido, H. Akiyama, H. Uesaka, Y. Enose, R. Horiuchi, T. Kuwata, T. Goto, H. Takahashi, and M. Hayami (2003)
J. Gen. Virol. 84, 2237-2244
   Abstract »    Full Text »    PDF »
AIDS vaccine: new ideas from old approaches.
A J Beale (2003)
J R Soc Med 96, 347-348
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Construction and in vivo infection of a new simian/human immunodeficiency virus chimera containing the reverse transcriptase gene and the 3' half of the genomic region of human immunodeficiency virus type 1.
H. Akiyama, E. Ido, W. Akahata, T. Kuwata, T. Miura, and M. Hayami (2003)
J. Gen. Virol. 84, 1663-1669
   Abstract »    Full Text »    PDF »
Determinants of Increased Replicative Capacity of Serially Passaged Simian Immunodeficiency Virus with nef Deleted in Rhesus Monkeys.
L. Alexander, P. O. Illyinskii, S. M. Lang, R. E. Means, J. Lifson, K. Mansfield, and R. C. Desrosiers (2003)
J. Virol. 77, 6823-6835
   Abstract »    Full Text »    PDF »
Expression of Simian Immunodeficiency Virus (SIV) Nef in Astrocytes during Acute and Terminal Infection and Requirement of Nef for Optimal Replication of Neurovirulent SIV In Vitro.
E. D. Overholser, G. D. Coleman, J. L. Bennett, R. J. Casaday, M. C. Zink, S. A. Barber, and J. E. Clements (2003)
J. Virol. 77, 6855-6866
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nef Gene Is Required for Robust Productive Infection by Simian Immunodeficiency Virus of T-Cell-Rich Paracortex in Lymph Nodes.
C. Sugimoto, K. Tadakuma, I. Otani, T. Moritoyo, H. Akari, F. Ono, Y. Yoshikawa, T. Sata, S. Izumo, and K. Mori (2003)
J. Virol. 77, 4169-4180
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Simian-Human Immunodeficiency Virus SHIV89.6-Induced Protection against Intravaginal Challenge with Pathogenic SIVmac239 Is Independent of the Route of Immunization and Is Associated with a Combination of Cytotoxic T-Lymphocyte and Alpha Interferon Responses.
K. Abel, L. Compton, T. Rourke, D. Montefiori, D. Lu, K. Rothaeusler, L. Fritts, K. Bost, and C. J. Miller (2003)
J. Virol. 77, 3099-3118
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Containment of Simian Immunodeficiency Virus Infection in Vaccinated Macaques: Correlation with the Magnitude of Virus-Specific Pre- and Postchallenge CD4+ and CD8+ T Cell Responses.
Z. Hel, J. Nacsa, E. Tryniszewska, W.-P. Tsai, R. W. Parks, D. C. Montefiori, B. K. Felber, J. Tartaglia, G. N. Pavlakis, and G. Franchini (2002)
J. Immunol. 169, 4778-4787
   Abstract »    Full Text »    PDF »
T-Cell Receptor:CD3 Down-Regulation Is a Selected In Vivo Function of Simian Immunodeficiency Virus Nef but Is Not Sufficient for Effective Viral Replication in Rhesus Macaques.
J. Munch, A. Janardhan, N. Stolte, C. Stahl-Hennig, P. ten Haaft, J. L. Heeney, T. Swigut, F. Kirchhoff, and J. Skowronski (2002)
J. Virol. 76, 12360-12364
   Abstract »    Full Text »    PDF »
Live, Attenuated Simian Immunodeficiency Virus SIVmac-M4, with Point Mutations in the Env Transmembrane Protein Intracytoplasmic Domain, Provides Partial Protection from Mucosal Challenge with Pathogenic SIVmac251.
B. L. Shacklett, K. E. S. Shaw, L. A. Adamson, D. T. Wilkens, C. A. Cox, D. C. Montefiori, M. B. Gardner, P. Sonigo, and P. A. Luciw (2002)
J. Virol. 76, 11365-11378
   Abstract »    Full Text »    PDF »
Effects of Cytotoxic T Lymphocytes (CTL) Directed against a Single Simian Immunodeficiency Virus (SIV) Gag CTL Epitope on the Course of SIVmac239 Infection.
T. M. Allen, P. Jing, B. Calore, H. Horton, D. H. O'Connor, T. Hanke, M. Piekarczyk, R. Ruddersdorf, B. R. Mothe, C. Emerson, et al. (2002)
J. Virol. 76, 10507-10511
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Design and tests of an HIV vaccine.
A. McMichael, M. Mwau, and T. Hanke (2002)
Br. Med. Bull. 62, 87-98
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Coreceptor Phenotype of Natural Human Immunodeficiency Virus with Nef Deleted Evolves In Vivo, Leading to Increased Virulence.
A. Jekle, B. Schramm, P. Jayakumar, V. Trautner, D. Schols, E. De Clercq, J. Mills, S. M. Crowe, and M. A. Goldsmith (2002)
J. Virol. 76, 6966-6973
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Immunization of Rhesus Macaques with a DNA Prime/Modified Vaccinia Virus Ankara Boost Regimen Induces Broad Simian Immunodeficiency Virus (SIV)-Specific T-Cell Responses and Reduces Initial Viral Replication but Does Not Prevent Disease Progression following Challenge with Pathogenic SIVmac239.
H. Horton, T. U. Vogel, D. K. Carter, K. Vielhuber, D. H. Fuller, T. Shipley, J. T. Fuller, K. J. Kunstman, G. Sutter, D. C. Montefiori, et al. (2002)
J. Virol. 76, 7187-7202
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Human Immunodeficiency Virus Type 1 Subtype C Molecular Phylogeny: Consensus Sequence for an AIDS Vaccine Design?.
V. Novitsky, U. R. Smith, P. Gilbert, M. F. McLane, P. Chigwedere, C. Williamson, T. Ndung'u, I. Klein, S. Y. Chang, T. Peter, et al. (2002)
J. Virol. 76, 5435-5451
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Detailed Analysis of CD4+ Th Responses to Envelope and Gag Proteins of Simian Immunodeficiency Virus Reveals an Exclusion of Broadly Reactive Th Epitopes from the Glycosylated Regions of Envelope.
S. Sarkar, V. Kalia, M. Murphey-Corb, and R. C. Montelaro (2002)
J. Immunol. 168, 4001-4011
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Tat-Vaccinated Macaques Do Not Control Simian Immunodeficiency Virus SIVmac239 Replication.
T. M. Allen, L. Mortara, B. R. Mothe, M. Liebl, P. Jing, B. Calore, M. Piekarczyk, R. Ruddersdorf, D. H. O'Connor, X. Wang, et al. (2002)
J. Virol. 76, 4108-4112
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Nef-Mediated Resistance of Human Immunodeficiency Virus Type 1 to Antiviral Cytotoxic T Lymphocytes.
O. O. Yang, P. T. Nguyen, S. A. Kalams, T. Dorfman, H. G. Gottlinger, S. Stewart, I. S. Y. Chen, S. Threlkeld, and B. D. Walker (2002)
J. Virol. 76, 1626-1631
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The Simian Immunodeficiency Virus {Delta}nef Vaccine, after Application to the Tonsils of Rhesus Macaques, Replicates Primarily within CD4+ T Cells and Elicits a Local Perforin-Positive CD8+ T-Cell Response.
C. Stahl-Hennig, R. M. Steinman, P. Ten Haaft, K. Uberla, N. Stolte, S. Saeland, K. Tenner-Racz, and P. Racz (2002)
J. Virol. 76, 688-696
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Dominance of CD8 Responses Specific for Epitopes Bound by a Single Major Histocompatibility Complex Class I Molecule during the Acute Phase of Viral Infection.
B. R. Mothe, H. Horton, D. K. Carter, T. M. Allen, M. E. Liebl, P. Skinner, T. U. Vogel, S. Fuenger, K. Vielhuber, W. Rehrauer, et al. (2002)
J. Virol. 76, 875-884
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Safety and Immunogenicity in Neonatal Mice of a Hyperattenuated Listeria Vaccine Directed against Human Immunodeficiency Virus.
M. Rayevskaya, N. Kushnir, and F. R. Frankel (2002)
J. Virol. 76, 918-922
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Rhabdovirus-Based Vectors with Human Immunodeficiency Virus Type 1 (HIV-1) Envelopes Display HIV-1-Like Tropism and Target Human Dendritic Cells.
H. D. Foley, M. Otero, J. M. Orenstein, R. J. Pomerantz, and M. J. Schnell (2002)
J. Virol. 76, 19-31
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Generation of Genome-Wide CD8 T Cell Responses in HLA-A*0201 Transgenic Mice by an HIV-1 Ubiquitin Expression Library Immunization Vaccine.
R. A. K. Singh, L. Wu, and M. A. Barry (2002)
J. Immunol. 168, 379-391
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Vaccination with Attenuated Simian Immunodeficiency Virus by DNA Inoculation.
S. J. Kent, C. J. Dale, S. Preiss, J. Mills, D. Campagna, and D. F. J. Purcell (2001)
J. Virol. 75, 11930-11934
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A Commonly Recognized Simian Immunodeficiency Virus Nef Epitope Presented to Cytotoxic T Lymphocytes of Indian-Origin Rhesus Monkeys by the Prevalent Major Histocompatibility Complex Class I Allele Mamu-A*02.
S. Robinson, W. A. Charini, M. H. Newberg, M. J. Kuroda, C. I. Lord, and N. L. Letvin (2001)
J. Virol. 75, 10179-10186
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Expression and Immunogenicity of Human Immunodeficiency Virus Type 1 Gag Expressed by a Replication-Competent Rhabdovirus-Based Vaccine Vector.
J. P. McGettigan, S. Sarma, J. M. Orenstein, R. J. Pomerantz, and M. J. Schnell (2001)
J. Virol. 75, 8724-8732
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Induction of Potent Human Immunodeficiency Virus Type 1-Specific T-Cell-Restricted Immunity by Genetically Modified Dendritic Cells.
J. Lisziewicz, D. I. Gabrilovich, G. Varga, J. Xu, P. D. Greenberg, S. K. Arya, M. Bosch, J.-P. Behr, and F. Lori (2001)
J. Virol. 75, 7621-7628
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Cross-protection against mucosal simian immunodeficiency virus (SIVsm) challenge in human immunodeficiency virus type 2-vaccinated cynomolgus monkeys.
L. Walther-Jallow, C. Nilsson, J. Soderlund, P. ten Haaft, B. Makitalo, P. Biberfeld, P. Bottiger, J. Heeney, G. Biberfeld, and R. Thorstensson (2001)
J. Gen. Virol. 82, 1601-1612
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Insertion/deletion frequencies match those of point mutations in the hypervariable regions of the simian immunodeficiency virus surface envelope gene.
R. Cheynier, L. Kils-Hutten, A. Meyerhans, and S. Wain-Hobson (2001)
J. Gen. Virol. 82, 1613-1619
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Reduction of Simian-Human Immunodeficiency Virus 89.6P Viremia in Rhesus Monkeys by Recombinant Modified Vaccinia Virus Ankara Vaccination.
D. H. Barouch, S. Santra, M. J. Kuroda, J. E. Schmitz, R. Plishka, A. Buckler-White, A. E. Gaitan, R. Zin, J.-H. Nam, L. S. Wyatt, et al. (2001)
J. Virol. 75, 5151-5158
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Construction and In Vitro Properties of a Series of Attenuated Simian Immunodeficiency Viruses with All Accessory Genes Deleted.
Y. Guan, J. B. Whitney, M. Detorio, and M. A. Wainberg (2001)
J. Virol. 75, 4056-4067
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Rabies Virus-Based Vectors Expressing Human Immunodeficiency Virus Type 1 (HIV-1) Envelope Protein Induce a Strong, Cross-Reactive Cytotoxic T-Lymphocyte Response against Envelope Proteins from Different HIV-1 Isolates.
J. P. McGettigan, H. D. Foley, I. M. Belyakov, J. A. Berzofsky, R. J. Pomerantz, and M. J. Schnell (2001)
J. Virol. 75, 4430-4434
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Novel, Live Attenuated Simian Immunodeficiency Virus Constructs Containing Major Deletions in Leader RNA Sequences.
Y. Guan, J. B. Whitney, C. Liang, and M. A. Wainberg (2001)
J. Virol. 75, 2776-2785
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Persistence of Pathogenic Challenge Virus in Macaques Protected by Simian Immunodeficiency Virus SIVmac{Delta}nef.
E. Khatissian, V. Monceaux, M.-C. Cumont, M.-P. Kieny, A.-M. Aubertin, and B. Hurtrel (2001)
J. Virol. 75, 1507-1515
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Negative Factor from SIV Binds to the Catalytic Subunit of the V-ATPase to Internalize CD4 and to Increase Viral Infectivity.
R. Mandic, O. T. Fackler, M. Geyer, T. Linnemann, Y.-H. Zheng, and B. M. Peterlin (2001)
Mol. Biol. Cell 12, 463-473
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CD8+ Lymphocytes from Simian Immunodeficiency Virus-Infected Rhesus Macaques Recognize 14 Different Epitopes Bound by the Major Histocompatibility Complex Class I Molecule Mamu-A*01: Implications for Vaccine Design and Testing.
T. M. Allen, B. R. Mothé, J. Sidney, P. Jing, J. L. Dzuris, M. E. Liebl, T. U. Vogel, D. H. O'Connor, X. Wang, M. C. Wussow, et al. (2001)
J. Virol. 75, 738-749
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Strict Control of Human Immunodeficiency Virus Type 1 Replication by a Genetic Switch: Tet for Tat.
K. Verhoef, G. Marzio, W. Hillen, H. Bujard, and B. Berkhout (2001)
J. Virol. 75, 979-987
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