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.

Porcine endemic diarrhea virus infection regulates long noncoding RNA expression

“…Some researchers also reported the distinctive kinetics of lncRNA expression profiles during infectious bursal disease virus and Marek's disease virus infections in chicken (He et al, 2015). It was shown that lncRNAs were also involved in HIV and influenza virus infections (Rice, 2015;Trypsteen et al, 2016;Winterling et al, 2014). These studies suggested that lncRNAs may be involved in regulating the interactions between the host response and viral infection.…”

Differential gene expression analysis tools exhibit substandard performance for long non-coding RNA–sequencing data

“…While they do not encode for proteins, lncRNAs are strong regulators of gene expression 3 . The discovery and study of lncRNAs is of major relevance to human health and disease because they represent an extensive, largely unexplored, and functional component of the genome [3][4][5][6][7] . In contrast to mRNAs, lncRNAs are generally expressed in low amounts, typically an order of magnitude lower than mRNA expression levels 2,5,[8][9][10] .…”

“…The discovery and study of lncRNAs is of major relevance to human health and disease because they represent an extensive, largely unexplored, and functional component of the genome [3][4][5][6][7] . In contrast to mRNAs, lncRNAs are generally expressed in low amounts, typically an order of magnitude lower than mRNA expression levels 2,5,[8][9][10] . Furthermore, several studies demonstrated that lncRNA expression levels are very noisy, which is a characteristic shared with low count data from massively parallel RNA sequencing [10][11][12][13] .…”

Involvement and Roles of Long Noncoding RNAs in the Molecular Mechanisms of Emerging and Reemerging Viral Infections

“…Several other lncRNAs have been reported for their putative roles in regulating HIV viral life cycle. To study the different expression patterns of lncRNA during viral life cycle, Trypsteen et al (2016) performed a transcriptome profiling during HIV integration, reverse transcription, and HIV particle production. They also investigated the roles of these lncRNAs and found their involvement in different pathways of cell cycle regulation including responses to DNA damage, apoptosis, and proteasomal and ubiquitination pathways (Trypsteen et al, 2016).…”

“…To study the different expression patterns of lncRNA during viral life cycle, Trypsteen et al (2016) performed a transcriptome profiling during HIV integration, reverse transcription, and HIV particle production. They also investigated the roles of these lncRNAs and found their involvement in different pathways of cell cycle regulation including responses to DNA damage, apoptosis, and proteasomal and ubiquitination pathways (Trypsteen et al, 2016). In addition, several lncRNAs have been reported to regulate gene expression through their interaction with chromatin modifying complexes, especially the polycomb repressor complex 2 (PRC2) that directs methylation marks to the promoters of targeted genes.…”