Differential expression of lncRNAs during the HIV replication cycle: an underestimated layer in the HIV-host interplay.

Abstract

Studying the effects of HIV infection on the host transcriptome has typically focused on protein-coding genes. However, recent advances in the field of RNA sequencing revealed that long non-coding RNAs (lncRNAs) add an extensive additional layer to the cell's molecular network. Here, we performed transcriptome profiling throughout a primary HIV infection in vitro to investigate lncRNA expression at the different HIV replication cycle processes (reverse transcription, integration and particle production). Subsequently, guilt-by-association, transcription factor and co-expression analysis were performed to infer biological roles for the lncRNAs identified in the HIV-host interplay. Many lncRNAs were suggested to play a role in mechanisms relying on proteasomal and ubiquitination pathways, apoptosis, DNA damage responses and cell cycle regulation. Through transcription factor binding analysis, we found that lncRNAs display a distinct transcriptional regulation profile as compared to protein coding mRNAs, suggesting that mRNAs and lncRNAs are independently modulated. In addition, we identified five differentially expressed lncRNA-mRNA pairs with mRNA involvement in HIV pathogenesis with possible cis regulatory lncRNAs that control nearby mRNA expression and function. Altogether, the present study demonstrates that lncRNAs add a new dimension to the HIV-host interplay and should be further investigated as they may represent targets for controlling HIV replication.

• Authors: Wim Trypsteen, Pejman Mohammadi, Clarissa Van Hecke, Pieter Mestdagh, Steve Lefever, Yvan Saeys, Pieter De Bleser, Jo Vandesompele, Angela Ciuffi, Linos Vandekerckhove, Ward De Spiegelaere
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 36111 (10 26 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27782208 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Long Noncoding
• RNA, Messenger

Topics

• CD4-Positive T-Lymphocytes (cytology, metabolism)
• Gene Expression Profiling
• Gene Regulatory Networks
• HIV (physiology)
• HIV Infections (genetics, pathology, virology)
• Humans
• Oligonucleotide Array Sequence Analysis
• RNA, Long Noncoding (genetics, metabolism)
• RNA, Messenger (metabolism)
• Virus Replication (genetics)