Acquisition of HIV-1 resistance in T lymphocytes using an ACA-specific E. coli mRNA interferase

Human Gene Therapy
Hideto ChonoIkunoshin Kato

Abstract

Transcriptional activation of gene expression directed by the long terminal repeat (LTR) of HIV-1 requires both the transactivation response element (TAR) and Tat protein. HIV-1 mutants lacking a functional tat gene are not able to proliferate. Here we take a genetic approach to suppress HIV-1 replication based on Tat-dependent production of MazF, an ACA-specific endoribonuclease (mRNA interferase) from Escherichia coli. When induced, MazF is known to cause Bak- and NBK-dependent apoptotic cell death in mammalian cells. We first constructed a retroviral vector, in which the mazF (ACA-less) gene was inserted under the control of the HIV-1 LTR, which was then transduced into CD4+ T-lymphoid CEM-SS cells in such a way that, upon HIV-1 infection, the mazF gene is induced to destroy the infecting HIV-1 mRNA, preventing HIV-1 replication. Indeed, when the transduced cells were infected with HIV-1 IIIB, the viral replication was effectively inhibited, as HIV-1 IIIB p24 could not be detected in the culture medium. Consistently, not only cell growth but also the CD4 level was not affected by the infection. These results suggest that the HIV-1-LTR-regulated mazF gene was effectively induced upon HIV-1 IIIB infection, which is sufficient ...Continue Reading

References

Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·S KimD Baltimore
May 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·S F YuE Gilboa
Aug 23, 1996·The Journal of Biological Chemistry·S K SaxenaR J Youle
Feb 20, 2003·Biochemistry·Robert H Silverman
Apr 8, 2004·Virus Research·Nan Sook Lee, John J Rossi
Apr 14, 2006·The Journal of Biological Chemistry·Ling ZhuMasayori Inouye
Jul 4, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sumit AgarwalNikunj V Somia
Nov 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Bruce L LevineCarl H June
Feb 14, 2009·Progress in Molecular Biology and Translational Science·Yoshihiro Yamaguchi, Masayori Inouye

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Citations

Feb 22, 2012·PLoS Computational Biology·Iraj Hosseini, Feilim Mac Gabhann
Jul 19, 2011·FEBS Letters·Jung-Ho ParkMasayori Inouye
May 8, 2015·Expert Opinion on Biological Therapy·Bruce LevineMegan Davis
Apr 6, 2016·Frontiers in Molecular Biosciences·Wai Ting ChanChew Chieng Yeo
Aug 9, 2011·Critical Reviews in Biochemistry and Molecular Biology·Finbarr Hayes, Laurence Van Melderen
Mar 23, 2015·FEMS Microbiology Reviews·Wai Ting ChanManuel Espinosa
Nov 20, 2013·Mobile Genetic Elements·Simon J UnterholznerWilfried Rozhon
Jan 15, 2015·Protein Expression and Purification·Yann G-J SterckxAbel Garcia-Pino
Jan 8, 2013·FEMS Microbiology Letters·Christopher F Schuster, Ralph Bertram
Jan 31, 2014·Pathogens and Disease·Yurong WenBart Devreese
Sep 20, 2011·Nature Reviews. Microbiology·Yoshihiro Yamaguchi, Masayori Inouye
Feb 28, 2019·Biomolecular Concepts·Alicia BravoManuel Espinosa
Apr 27, 2017·Oncotarget·Shiran ShapiraNadir Arber
Jun 10, 2020·Chembiochem : a European Journal of Chemical Biology·Shahrzad Jahanshahi, Yingfu Li
Sep 10, 2020·Toxins·Marcin RównickiDariusz Bartosik
Nov 11, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jennifer Viegas
Nov 14, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jeffrey M JacobsonCarl H June
Feb 15, 2021·Applied Microbiology and Biotechnology·Akriti SrivastavaLalit C Garg
Oct 22, 2020·Synthetic and Systems Biotechnology·Wenhui Zhang, Qiong Wu
Jun 18, 2021·Nucleic Acids Research·Gabriela Garcia-RodriguezRemy Loris

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Methods Mentioned

BETA
PCR
transfection
ELISA
flow cytometry

Software Mentioned

FACSDiva
Excel

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