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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  kyouindb  KAKEN_id  orcid 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  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-5415-1352 (unconfirmed)
Battivelli, Emilie
Verdin, Eric
Koyanagi, Yoshio  kyouindb  KAKEN_id  orcid 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

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