Deep Sequencing of HIV-Infected Cells: Insights into Nascent Transcription and Host-Directed Therapy

作者：Peng, Xinxia; Sova, Pavel; Green, Richard R.; Thomas, Matthew J.; Korth, Marcus J.; Proll, Sean; Xu, Jiabao; Cheng, Yanbing; Yi, Kang; Chen, Li; Peng, Zhiyu; Wang, Jun; Palermo, Robert E.; Katze, Michael G.^*

来源：Journal of Virology, 2014, 88(16): 8768-8782.

DOI：10.1128/JVI.00768-14

• IMMUNODEFICIENCY-VIRUS TYPE-1
• NONCODING RNAS
• EXPRESSION
• REVEALS
• QUANTIFICATION
• ANNOTATION
• DYNAMICS
• GENES
• BLOOD

Polyadenylated mature mRNAs are the focus of standard transcriptome analyses. However, the profiling of nascent transcripts, which often include nonpolyadenylated RNAs, can unveil novel insights into transcriptional regulation. Here, we separately sequenced total RNAs (Total RNAseq) and mRNAs (mRNAseq) from the same HIV-1-infected human CD4(+) T cells. We found that many nonpolyadenylated RNAs were differentially expressed upon HIV-1 infection, and we identified 8 times more differentially expressed genes at 12 h postinfection by Total RNAseq than by mRNAseq. These expression changes were also evident by concurrent changes in introns and were recapitulated by later mRNA changes, revealing an unexpectedly significant delay between transcriptional initiation and mature mRNA production early after HIV-1 infection. We computationally derived and validated the underlying regulatory programs, and we predicted drugs capable of reversing these HIV-1-induced expression changes followed by experimental confirmation. Our results show that combined total and mRNA transcriptome analysis is essential for fully capturing the early host response to virus infection and provide a framework for identifying candidate drugs for host-directed therapy against HIV/AIDS.

• 出版日期2014-8
• 单位深圳华大生命科学研究院