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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.

Author information

1
Department of Internal Medicine, HIV Cure Research Centre, Ghent University, Ghent, Belgium.
2
Institute of Microbiology (IMUL), Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
3
Center Medical Genetics, Ghent University, Belgium.
4
Inflammation Research Center, Flanders Institute of Biotechnology (VIB), Ghent, Belgium.
5
Department of Biomedical Molecular Biology Ghent University, Ghent, Belgium.
6
Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
7
Department of Morphology, Ghent University, Belgium.

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.

PMID:
27782208
PMCID:
PMC5080576
DOI:
10.1038/srep36111
[Indexed for MEDLINE]
Free PMC Article

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