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, researchers from Ghent University 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, the researchers 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.
Overview of the guilt-by-association analysis
(A) Network representation of differentially expressed lncRNAs at the 6 h (purple dots), 18 h (green dots) and 30 h (blue dots) time point. lncRNAs are represented in the outer circle and connected pathways (red dots) at the inside of the circle. Connections show a negative association (red line) or a positive association (green line). The size of all circles is scaled to the number of connections. (B) Overview of lncRNA associations (columns) with 33 significantly enriched Biocarta pathways (rows). A negative association (red rectangles) and positive association (blue rectangles) are represented. Pathways are clustered according to the number of mutual genes.