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Title: | CAGE-Seq Reveals that HIV-1 Latent Infection Does Not Trigger Unique Cellular Responses in a Jurkat T Cell Model |
Authors: | Matsui, Hiroyuki Shirakawa, Kotaro https://orcid.org/0000-0002-7469-1276 (unconfirmed) Konishi, Yoshinobu Hirabayashi, Shigeki Sarca, Anamaria Daniela Fukuda, Hirofumi Nomura, Ryosuke Stanford, Emani Horisawa, Yoshihito Kazuma, Yasuhiro Matsumoto, Tadahiko Yamazaki, Hiroyuki Murakawa, Yasuhiro https://orcid.org/0000-0002-5415-1352 (unconfirmed) Battivelli, Emilie Verdin, Eric Koyanagi, Yoshio https://orcid.org/0000-0002-3007-6642 (unconfirmed) Takaori-Kondo, Akifumi |
Author's alias: | 松井, 宏行 白川, 康太郎 小西, 義延 平林, 茂樹 福田, 寛文 野村, 亮介 堀澤, 欣史 数馬, 安浩 松本, 忠彦 山崎, 寛章 村川, 泰裕 小柳, 義夫 髙折, 晃史 |
Keywords: | CAGE-seq HIV-1 gene expression latency |
Issue Date: | 25-Mar-2021 |
Publisher: | American Society for Microbiology |
Journal title: | Journal of Virology |
Volume: | 95 |
Issue: | 8 |
Thesis number: | e02394-20 |
Abstract: | 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 (EF1α) 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 non-infected 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. |
Rights: | © 2021 Matsui et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. |
URI: | http://hdl.handle.net/2433/276870 |
DOI(Published Version): | 10.1128/JVI.02394-20 |
PubMed ID: | 33504604 |
Appears in Collections: | Journal Articles |
This item is licensed under a Creative Commons License