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Sci Rep. 2016 Oct 26;6:36111. doi: 10.1038/srep36111.

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

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Department of Internal Medicine, HIV Cure Research Centre, Ghent University, Ghent, Belgium.
Institute of Microbiology (IMUL), Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Center Medical Genetics, Ghent University, Belgium.
Inflammation Research Center, Flanders Institute of Biotechnology (VIB), Ghent, Belgium.
Department of Biomedical Molecular Biology Ghent University, Ghent, Belgium.
Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
Department of Morphology, Ghent University, Belgium.


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.

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