Induction of E. coli-derived endonuclease MazF suppresses HIV-1 production and causes apoptosis in latently infected cells
Copyright © 2020 Elsevier Inc. All rights reserved..
The current antiretroviral therapy cannot cure the patients infected with human immunodeficiency virus type 1 (HIV-1) due to the existence of latently infected cells capable of virus production from harboring proviral DNA. MazF is an ACA nucleotide sequence-specific endoribonuclease derived from Escherichia coli. The conditional expression of MazF by binding of HIV-1 Tat to the promoter region of a MazF-expression vector has previously been shown to selectively inhibit HIV-1 replication in acutely infected cells. The expression of MazF significantly suppressed tumor necrosis factor (TNF)-α-induced HIV-1 production and viral RNA expression in the HIV-1 latently infected cell line OM-10.1 transduced with the MazF-expression vector (OM-10.1/MFR). Moreover, the viability of OM-10.1/MFR cells decreased with increasing concentrations of TNF-α, whereas such decrease was not observed for HL-60 cells transduced with the MazF-expression vector (HL-60/MFR), the uninfected parental cell line of OM-10.1. TNF-α increased the expression of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase in OM-10.1/MFR cells, indicating that the cell death was caused by the induction of apoptosis. TNF-α-induced expression of MazF mRNA was detected in OM-10.1/MFR but not HL-60/MFR cells, suggesting that TNF-α-induced apoptosis of latently infected cells was due to the expression of MazF. Thus, the anti-HIV-1 gene therapy using the MazF-expression vector may have potential for the cure of HIV-1 infection in combination with suitable latency reversing agents through reducing the size of latently infected cells without viral reactivation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:530 |
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| Enthalten in: |
Biochemical and biophysical research communications - 530(2020), 3 vom: 24. Sept., Seite 597-602 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Okamoto, Mika [VerfasserIn] |
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| Links: |
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| Themen: |
Apoptosis |
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| Anmerkungen: |
Date Completed 16.03.2021 Date Revised 16.03.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2020.07.103 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM313224021 |
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| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a The current antiretroviral therapy cannot cure the patients infected with human immunodeficiency virus type 1 (HIV-1) due to the existence of latently infected cells capable of virus production from harboring proviral DNA. MazF is an ACA nucleotide sequence-specific endoribonuclease derived from Escherichia coli. The conditional expression of MazF by binding of HIV-1 Tat to the promoter region of a MazF-expression vector has previously been shown to selectively inhibit HIV-1 replication in acutely infected cells. The expression of MazF significantly suppressed tumor necrosis factor (TNF)-α-induced HIV-1 production and viral RNA expression in the HIV-1 latently infected cell line OM-10.1 transduced with the MazF-expression vector (OM-10.1/MFR). Moreover, the viability of OM-10.1/MFR cells decreased with increasing concentrations of TNF-α, whereas such decrease was not observed for HL-60 cells transduced with the MazF-expression vector (HL-60/MFR), the uninfected parental cell line of OM-10.1. TNF-α increased the expression of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase in OM-10.1/MFR cells, indicating that the cell death was caused by the induction of apoptosis. TNF-α-induced expression of MazF mRNA was detected in OM-10.1/MFR but not HL-60/MFR cells, suggesting that TNF-α-induced apoptosis of latently infected cells was due to the expression of MazF. Thus, the anti-HIV-1 gene therapy using the MazF-expression vector may have potential for the cure of HIV-1 infection in combination with suitable latency reversing agents through reducing the size of latently infected cells without viral reactivation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Gene therapy | |
| 650 | 4 | |a HIV-1 | |
| 650 | 4 | |a Latent infection | |
| 650 | 4 | |a MazF | |
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| 650 | 7 | |a Escherichia coli Proteins |2 NLM | |
| 650 | 7 | |a MazF protein, E coli |2 NLM | |
| 650 | 7 | |a Endoribonucleases |2 NLM | |
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| 700 | 1 | |a Hidaka, Akemi |e verfasserin |4 aut | |
| 700 | 1 | |a Toyama, Masaaki |e verfasserin |4 aut | |
| 700 | 1 | |a Mineno, Junichi |e verfasserin |4 aut | |
| 700 | 1 | |a Baba, Masanori |e verfasserin |4 aut | |
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