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HIV LTR-Driven Antisense RNA by Itself Has Regulatory Function and May Curtail Virus Reactivation From Latency

Latently infected T lymphocytes are an important barrier toward eliminating a persistent HIV infection. Here we describe an HIV-based recombinant fluorescent-lentivirus referred to as “rfl-HIV” that enables to analyze sense and antisense transcription by means of fluorescence reporter genes. This mo...

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Autores principales: Kobayashi-Ishihara, Mie, Terahara, Kazutaka, Martinez, Javier P., Yamagishi, Makoto, Iwabuchi, Ryutaro, Brander, Christian, Ato, Manabu, Watanabe, Toshiki, Meyerhans, Andreas, Tsunetsugu-Yokota, Yasuko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980963/
https://www.ncbi.nlm.nih.gov/pubmed/29887842
http://dx.doi.org/10.3389/fmicb.2018.01066
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author Kobayashi-Ishihara, Mie
Terahara, Kazutaka
Martinez, Javier P.
Yamagishi, Makoto
Iwabuchi, Ryutaro
Brander, Christian
Ato, Manabu
Watanabe, Toshiki
Meyerhans, Andreas
Tsunetsugu-Yokota, Yasuko
author_facet Kobayashi-Ishihara, Mie
Terahara, Kazutaka
Martinez, Javier P.
Yamagishi, Makoto
Iwabuchi, Ryutaro
Brander, Christian
Ato, Manabu
Watanabe, Toshiki
Meyerhans, Andreas
Tsunetsugu-Yokota, Yasuko
author_sort Kobayashi-Ishihara, Mie
collection PubMed
description Latently infected T lymphocytes are an important barrier toward eliminating a persistent HIV infection. Here we describe an HIV-based recombinant fluorescent-lentivirus referred to as “rfl-HIV” that enables to analyze sense and antisense transcription by means of fluorescence reporter genes. This model virus exhibited similar transcriptional and functional properties of the antisense transcript as observed with a wild type HIV, and largely facilitated the generation of latently-infected T cells clones. We show that latently-infected cells can be divided into two types, those with and those without antisense transcription. Upon addition of latency reversal agents, only the cells that lack antisense transcripts are readily reactivated to transcribe HIV. Thus, antisense transcripts may exhibit a dominant suppressor activity and can lock an integrated provirus into a non-reactivatable state. These findings could have important implications for the development of strategies to eradicate HIV from infected individuals.
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spelling pubmed-59809632018-06-08 HIV LTR-Driven Antisense RNA by Itself Has Regulatory Function and May Curtail Virus Reactivation From Latency Kobayashi-Ishihara, Mie Terahara, Kazutaka Martinez, Javier P. Yamagishi, Makoto Iwabuchi, Ryutaro Brander, Christian Ato, Manabu Watanabe, Toshiki Meyerhans, Andreas Tsunetsugu-Yokota, Yasuko Front Microbiol Microbiology Latently infected T lymphocytes are an important barrier toward eliminating a persistent HIV infection. Here we describe an HIV-based recombinant fluorescent-lentivirus referred to as “rfl-HIV” that enables to analyze sense and antisense transcription by means of fluorescence reporter genes. This model virus exhibited similar transcriptional and functional properties of the antisense transcript as observed with a wild type HIV, and largely facilitated the generation of latently-infected T cells clones. We show that latently-infected cells can be divided into two types, those with and those without antisense transcription. Upon addition of latency reversal agents, only the cells that lack antisense transcripts are readily reactivated to transcribe HIV. Thus, antisense transcripts may exhibit a dominant suppressor activity and can lock an integrated provirus into a non-reactivatable state. These findings could have important implications for the development of strategies to eradicate HIV from infected individuals. Frontiers Media S.A. 2018-05-25 /pmc/articles/PMC5980963/ /pubmed/29887842 http://dx.doi.org/10.3389/fmicb.2018.01066 Text en Copyright © 2018 Kobayashi-Ishihara, Terahara, Martinez, Yamagishi, Iwabuchi, Brander, Ato, Watanabe, Meyerhans and Tsunetsugu-Yokota. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Kobayashi-Ishihara, Mie
Terahara, Kazutaka
Martinez, Javier P.
Yamagishi, Makoto
Iwabuchi, Ryutaro
Brander, Christian
Ato, Manabu
Watanabe, Toshiki
Meyerhans, Andreas
Tsunetsugu-Yokota, Yasuko
HIV LTR-Driven Antisense RNA by Itself Has Regulatory Function and May Curtail Virus Reactivation From Latency
title HIV LTR-Driven Antisense RNA by Itself Has Regulatory Function and May Curtail Virus Reactivation From Latency
title_full HIV LTR-Driven Antisense RNA by Itself Has Regulatory Function and May Curtail Virus Reactivation From Latency
title_fullStr HIV LTR-Driven Antisense RNA by Itself Has Regulatory Function and May Curtail Virus Reactivation From Latency
title_full_unstemmed HIV LTR-Driven Antisense RNA by Itself Has Regulatory Function and May Curtail Virus Reactivation From Latency
title_short HIV LTR-Driven Antisense RNA by Itself Has Regulatory Function and May Curtail Virus Reactivation From Latency
title_sort hiv ltr-driven antisense rna by itself has regulatory function and may curtail virus reactivation from latency
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980963/
https://www.ncbi.nlm.nih.gov/pubmed/29887842
http://dx.doi.org/10.3389/fmicb.2018.01066
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