Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice.
Stable integration of HIV proviral DNA into host cell chromosomes, a hallmark and essential feature of the retroviral life cycle, establishes the infection permanently. Current antiretroviral combination drug therapy cannot cure HIV infection. However, expressing an engineered HIV-1 long terminal re...
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2013
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oai:doaj.org-article:a30385a2f1f846a49457496bcee834272021-11-18T06:07:35ZHighly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice.1553-73661553-737410.1371/journal.ppat.1003587https://doaj.org/article/a30385a2f1f846a49457496bcee834272013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086129/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Stable integration of HIV proviral DNA into host cell chromosomes, a hallmark and essential feature of the retroviral life cycle, establishes the infection permanently. Current antiretroviral combination drug therapy cannot cure HIV infection. However, expressing an engineered HIV-1 long terminal repeat (LTR) site-specific recombinase (Tre), shown to excise integrated proviral DNA in vitro, may provide a novel and highly promising antiviral strategy. We report here the conditional expression of Tre-recombinase from an advanced lentiviral self-inactivation (SIN) vector in HIV-infected cells. We demonstrate faithful transgene expression, resulting in accurate provirus excision in the absence of cytopathic effects. Moreover, pronounced Tre-mediated antiviral effects are demonstrated in vivo, particularly in humanized Rag2⁻/⁻γc⁻/⁻ mice engrafted with either Tre-transduced primary CD4⁺ T cells, or Tre-transduced CD34⁺ hematopoietic stem and progenitor cells (HSC). Taken together, our data support the use of Tre-recombinase in novel therapy strategies aiming to provide a cure for HIV.Ilona HauberHelga Hofmann-SieberJan ChemnitzDanilo DubrauJanet ChusainowRolf StuckaPhilip HartjenAxel SchambachPatrick ZieglerKarl HackmannEvelin SchröckUdo SchumacherChristoph LindnerAdam GrundhoffChristopher BaumMarkus G ManzFrank BuchholzJoachim HauberPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 9, p e1003587 (2013) |
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| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Ilona Hauber Helga Hofmann-Sieber Jan Chemnitz Danilo Dubrau Janet Chusainow Rolf Stucka Philip Hartjen Axel Schambach Patrick Ziegler Karl Hackmann Evelin Schröck Udo Schumacher Christoph Lindner Adam Grundhoff Christopher Baum Markus G Manz Frank Buchholz Joachim Hauber Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice. |
| description |
Stable integration of HIV proviral DNA into host cell chromosomes, a hallmark and essential feature of the retroviral life cycle, establishes the infection permanently. Current antiretroviral combination drug therapy cannot cure HIV infection. However, expressing an engineered HIV-1 long terminal repeat (LTR) site-specific recombinase (Tre), shown to excise integrated proviral DNA in vitro, may provide a novel and highly promising antiviral strategy. We report here the conditional expression of Tre-recombinase from an advanced lentiviral self-inactivation (SIN) vector in HIV-infected cells. We demonstrate faithful transgene expression, resulting in accurate provirus excision in the absence of cytopathic effects. Moreover, pronounced Tre-mediated antiviral effects are demonstrated in vivo, particularly in humanized Rag2⁻/⁻γc⁻/⁻ mice engrafted with either Tre-transduced primary CD4⁺ T cells, or Tre-transduced CD34⁺ hematopoietic stem and progenitor cells (HSC). Taken together, our data support the use of Tre-recombinase in novel therapy strategies aiming to provide a cure for HIV. |
| format |
article |
| author |
Ilona Hauber Helga Hofmann-Sieber Jan Chemnitz Danilo Dubrau Janet Chusainow Rolf Stucka Philip Hartjen Axel Schambach Patrick Ziegler Karl Hackmann Evelin Schröck Udo Schumacher Christoph Lindner Adam Grundhoff Christopher Baum Markus G Manz Frank Buchholz Joachim Hauber |
| author_facet |
Ilona Hauber Helga Hofmann-Sieber Jan Chemnitz Danilo Dubrau Janet Chusainow Rolf Stucka Philip Hartjen Axel Schambach Patrick Ziegler Karl Hackmann Evelin Schröck Udo Schumacher Christoph Lindner Adam Grundhoff Christopher Baum Markus G Manz Frank Buchholz Joachim Hauber |
| author_sort |
Ilona Hauber |
| title |
Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice. |
| title_short |
Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice. |
| title_full |
Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice. |
| title_fullStr |
Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice. |
| title_full_unstemmed |
Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice. |
| title_sort |
highly significant antiviral activity of hiv-1 ltr-specific tre-recombinase in humanized mice. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/a30385a2f1f846a49457496bcee83427 |
| work_keys_str_mv |
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| _version_ |
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