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

Keywords

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

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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    Kobayashi-Ishihara, M., Terahara, K., Martinez, J. P., 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, 9(MAY), [1066]. https://doi.org/10.3389/fmicb.2018.01066