Integrated Single-cell Multiomic Analysis of HIV Latency Reversal Reveals Novel Regulators of Viral Reactivation

作     者：Manickam Ashokkumar Wenwen Mei Jackson J.Peterson Yuriko Harigaya David M.Murdoch David M.Margolis Caleb Kornfein Alex Oesterling Zhicheng Guo Cynthia D.Rudin Yuchao Jiang Edward P.Browne 

作者机构：Department of MedicineUniversity of North Carolina at Chapel HillChapel HillNC 27599USA HIV Cure CenterUniversity of North Carolina at Chapel HillChapel HillNC 27599USA Department of BiostatisticsUniversity of North Carolina at Chapel HillChapel HillNC 27599USA Department of Microbiology and ImmunologyUniversity of North Carolina at Chapel HillChapel HillNC 27599USA Department of GeneticsUniversity of North Carolina at Chapel HillChapel HillNC 27599USA Department of MedicineDuke UniversityDurhamNC 27708USA Department of Computer ScienceDuke UniversityDurhamNC 27708USA Department of StatisticsTexas A&M UniversityCollege StationTX 77843USA Department of BiologyTexas A&M UniversityCollege StationTX 77843USA Department of Biomedical EngineeringTexas A&M UniversityCollege StationTX 77843USA 

出 版 物：《Genomics, Proteomics & Bioinformatics》 (基因组蛋白质组与生物信息学报（英文版）)

年 卷 期：2024年第22卷第1期

页      面：67-88页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：supported by the following grants from the National Institutes of Health:the National Institute of Allergy and Infectious Diseases(NIAID)(Grant No.R01 AI143381)to Edward P.Browne the NIAID(Grant No.UM1 AI164567)to David M.Murdoch,the National Institute on Drug Abuse(NIDA)(Grant No.R61 DA047023)to Edward P.Browne the NIAID(Grant No.T32 AI007419)to Jackson J.Peterson the UNC-Chapel Hill Molecular Biology of Viral Diseases T32 to Jackson J.Peterson,the National Institute of General Medical Sciences(NIGMS)(Grant No.R35 GM138342)to Yuchao Jiang the NIDA(Grant No.R01 DA054994)to Cynthia D.Rudin 

主　　题：HIV latency reversal Primary CD4þT cell Single-cell multiomics HIV-regulating factor Machine learning 

摘      要：Despite the success of antiretroviral therapy,human immunodeficiency virus(HIV)cannot be cured because of a reservoir of latently infected cells that evades *** understand the mechanisms of HIV latency,we employed an integrated single-cell RNA sequencing(scRNA-seq)and single-cell assay for transposase-accessible chromatin with sequencing(scATAC-seq)approach to simultaneously profile the transcriptomic and epigenomic characteristics of~125,000 latently infected primary CD4^(+)T cells after reactivation using three different latency reversing *** expressed genes and differentially accessible motifs were used to examine transcriptional pathways and transcription factor(TF)activities across the cell *** identified cellular transcripts and TFs whose expression/activity was correlated with viral reactivation and demonstrated that a machine learning model trained on these data was 75%-79%accurate at predicting viral ***,we validated the role of two candidate HIV-regulating factors,FOXP1 and GATA3,in viral *** data demonstrate the power of integrated multimodal single-cell analysis to uncover novel relationships between host cell factors and HIV latency.