lncRNAs add a new dimension to the HIV-host interplay

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.

Trypsteen W, Mohammadi P, Van Hecke C, Mestdagh P, Lefever S, Saeys Y, De Bleser P, Vandesompele J, Ciuffi A, Vandekerckhove L, De Spiegelaere W. (2016) Differential expression of lncRNAs during the HIV replication cycle: an underestimated layer in the HIV-host interplay. Sci Rep 6:36111. [article]

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