期刊
VIRULENCE
卷 13, 期 1, 页码 386-413出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/21505594.2022.2031583
关键词
HIV-1; macrophages; single cell RNA sequencing; infection; pre-integrated cDNA complex transcription; provirus transcription
资金
- University of Utah [U01TW008163]
- [R21 AI124823]
HIV-1 cDNA pre-integration complexes can persist and remain transcriptionally active in macrophages for weeks. Single-cell RNA sequencing reveals distinct transcriptome patterns between cells harboring pre-integration complexes and integrated provirus cells. In addition, the presence of HIV-1 alters the transcriptome of uninfected bystander cells, differentiating them from true control cells.
HIV-1 cDNA pre-integration complexes persist for weeks in macrophages and remain transcriptionally active. While previous work has focused on the transcription of HIV-1 genes; our understanding of the cellular milieu that accompanies viral production is incomplete. We have used an in vitro system to model HIV-1 infection of macrophages, and single-cell RNA sequencing (scRNA-seq) to compare the transcriptomes of uninfected cells, cells harboring pre-integration complexes (PIC), and those containing integrated provirus and making late HIV proteins. scRNA-seq can distinguish between provirus and PIC cells because their background transcriptomes vary dramatically. PIC cell transcriptomes are characterized by NFkB and AP-1 promoted transcription, while transcriptomes of cells transcribing from provirus are characterized by E2F family transcription products. We also find that the transcriptomes of PIC cells and Bystander cells (defined as cells not producing any HIV transcript and thus presumably not infected) are indistinguishable except for the presence of HIV-1 transcripts. Furthermore, the presence of pathogen alters the transcriptome of the uninfected Bystander cells, so that they are distinguishable from true control cells (cells not exposed to any pathogen). Therefore, a single cell comparison of transcriptomes from provirus and PIC cells provides a new understanding of the transcriptional changes that accompany HIV-1 integration.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据