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 language | English |
|---|---|
| Article number | 1066 |
| Journal | Frontiers in Microbiology |
| Volume | 9 |
| Issue number | MAY |
| DOIs | |
| Publication status | Published - 2018 May 25 |
| Externally published | Yes |
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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 journal › Article
}
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 -