CAGE-seq reveals that HIV-1 latent infection does not trigger unique cellular responses in a jurkat T cell model

Hiroyuki Matsui, Kotaro Shirakawa, Yoshinobu Konishi, Shigeki Hirabayashi, Anamaria Daniela Sarca, Hirofumi Fukuda, Ryosuke Nomura, Emani Stanford, Yoshihito Horisawa, Yasuhiro Kazuma, Tadahiko Matsumoto, Hiroyuki Yamazaki, Yasuhiro Murakawa, Emilie Battivelli, Eric Verdin, Yoshio Koyanagi, Akifumi Takaori-Kondo

研究成果: Contribution to journalArticle査読

抄録

The cure for HIV-1 is currently stalled by our inability to specifically identify and target latently infected cells. HIV-1 viral RNA/DNA or viral proteins are recognized by cellular mechanisms and induce interferon responses in virus-producing cells, but changes in latently infected cells remain unknown. HIVGKO contains a green fluorescent protein (GFP) reporter under the HIV-1 promoter and a monomeric Kusabira orange 2 (mKO2) reporter under the internal elongation factor alpha (EF1a) promoter. This viral construct enables direct identification of both productively and latently HIV-1-infected cells. In this study, we aim to identify specific cellular transcriptional responses triggered by HIV-1 entry and integration using cap analysis of gene expression (CAGE). We deep sequenced CAGE tags in non-infected and latently and productively infected cells and compared their differentially expressed transcription start site (TSS) profiles. Virus-producing cells had differentially expressed TSSs related to T-cell activation and apoptosis compared to those of non-infected cells or latently infected cells. Surprisingly, latently infected cells had only 33 differentially expressed TSSs compared to those of noninfected cells. Among these, SPP1 and APOE were downregulated in latently infected cells. SPP1 or APOE knockdown in Jurkat T cells increased susceptibility to HIVGKO infection, suggesting that they have antiviral properties. Components of the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway, MLST8, 4EBP, and RPS6, were significant TSSs in productively infected cells, and S6 kinase (S6K) phosphorylation was increased compared to that in latently infected cells, suggesting that mTOR pathway activity plays a role in establishing the latent reservoir. These findings indicate that HIV-1 entry and integration do not trigger unique transcriptional responses when infection becomes latent.

本文言語英語
論文番号e02394
ジャーナルJournal of virology
95
8
DOI
出版ステータス出版済み - 4 2021
外部発表はい

All Science Journal Classification (ASJC) codes

  • 微生物学
  • 免疫学
  • 昆虫科学
  • ウイルス学

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