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2021 Fiscal Year Final Research Report

Transcriptome analysis of HIV-1 latently infected cells

Research Project

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Project/Area Number 19K07591
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionKyoto University

Principal Investigator

Shirakawa Kotaro  京都大学, 医学研究科, 助教 (80728270)

Project Period (FY) 2019-04-01 – 2022-03-31
KeywordsHIV潜伏感染 / トランスクリプトーム / CRISPRスクリーニング / mTOR経路
Outline of Final Research Achievements

HIVGKO enables direct identification of both productively and latently HIV-infected cells. In this study, we deep sequenced CAGE tags in non-infected and latently and productively infected cells and compared their transcriptional profiles. We detected 31 down regulated genes in latently infected cells 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 mTOR pathway were significantly up regulated in productively infected cells, suggesting that mTOR pathway activity plays a role in establishing the latent reservoir. These findings indicate that HIV entry and integration do not trigger unique transcriptional responses when infection becomes latent and that T cells cannot recognize the integrated HIV genome when infection remains latent.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

HIV感染症は抗ウイルス薬によりコントロール可能となったが、治療を中止すると再発してしまう。これはメモリーT細胞などのHIV潜伏感染細胞がウイルス蛋白を発現せず免疫による監視を生き残るためである。本研究ではHIV潜伏感染細胞の転写プロファイルを比較し、HIVゲノムがインテグレーションされた潜伏感染細胞に転写レベルで非感染細胞との差がほとんどないことを示された。本細胞モデルを用いてさらに潜伏感染の分子機構を明らかにできれば潜伏感染細胞を標的とした治癒を目指すための新たな治療法につながると考えられる。

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Published: 2023-01-30  

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