HIV LTR-driven antisense RNA by itself has regulatory function and may curtail virus reactivation from latency

Mie Kobayashi-Ishihara, Kazutaka Terahara, Javier P. Martinez, Makoto Yamagishi, Ryutaro Iwabuchi, Christian Brander, Manabu Ato, Toshiki Watanabe, Andreas Meyerhans, Yasuko Tsunetsugu-Yokota

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1066
JournalFrontiers in Microbiology
Volume9
Issue numberMAY
DOIs
Publication statusPublished - 2018 May 25
Externally publishedYes

Fingerprint

Virus Latency
Antisense RNA
HIV
T-Lymphocytes
Proviruses
Lentivirus
Reporter Genes
HIV Infections
Clone Cells
Fluorescence
Viruses

Keywords

  • HIV
  • Latency
  • Latency reversing agents
  • Reactivation
  • Viral antisense RNA

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

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.

In: Frontiers in Microbiology, Vol. 9, No. MAY, 1066, 25.05.2018.

Research output: Contribution to journalArticle

Kobayashi-Ishihara, M, Terahara, K, Martinez, JP, Yamagishi, M, Iwabuchi, R, Brander, C, Ato, M, Watanabe, T, Meyerhans, A & Tsunetsugu-Yokota, Y 2018, 'HIV LTR-driven antisense RNA by itself has regulatory function and may curtail virus reactivation from latency', Frontiers in Microbiology, vol. 9, no. MAY, 1066. https://doi.org/10.3389/fmicb.2018.01066
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. In: Frontiers in Microbiology. 2018 ; Vol. 9, No. MAY.
@article{6f4e32a88061488e81c3f06c931aa008,
title = "HIV LTR-driven antisense RNA by itself has regulatory function and may curtail virus reactivation from latency",
abstract = "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.",
keywords = "HIV, Latency, Latency reversing agents, Reactivation, Viral antisense RNA",
author = "Mie Kobayashi-Ishihara and Kazutaka Terahara and Martinez, {Javier P.} and Makoto Yamagishi and Ryutaro Iwabuchi and Christian Brander and Manabu Ato and Toshiki Watanabe and Andreas Meyerhans and Yasuko Tsunetsugu-Yokota",
year = "2018",
month = "5",
day = "25",
doi = "10.3389/fmicb.2018.01066",
language = "English",
volume = "9",
journal = "Frontiers in Microbiology",
issn = "1664-302X",
publisher = "Frontiers Media S. A.",
number = "MAY",

}

TY - JOUR

T1 - HIV LTR-driven antisense RNA by itself has regulatory function and may curtail virus reactivation from latency

AU - Kobayashi-Ishihara, Mie

AU - Terahara, Kazutaka

AU - Martinez, Javier P.

AU - Yamagishi, Makoto

AU - Iwabuchi, Ryutaro

AU - Brander, Christian

AU - Ato, Manabu

AU - Watanabe, Toshiki

AU - Meyerhans, Andreas

AU - Tsunetsugu-Yokota, Yasuko

PY - 2018/5/25

Y1 - 2018/5/25

N2 - 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.

AB - 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.

KW - HIV

KW - Latency

KW - Latency reversing agents

KW - Reactivation

KW - Viral antisense RNA

UR - http://www.scopus.com/inward/record.url?scp=85047537572&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047537572&partnerID=8YFLogxK

U2 - 10.3389/fmicb.2018.01066

DO - 10.3389/fmicb.2018.01066

M3 - Article

AN - SCOPUS:85047537572

VL - 9

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

SN - 1664-302X

IS - MAY

M1 - 1066

ER -