title: 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.
authors: Department of Internal Medicine, HIV Cure Research Centre, Ghent University, Ghent, Belgium.
authors: Wim
authors: W
authors: Trypsteen
authors: Institute of Microbiology (IMUL), Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
authors: Pejman
authors: P
authors: Mohammadi
authors: Department of Internal Medicine, HIV Cure Research Centre, Ghent University, Ghent, Belgium.
authors: Clarissa
authors: C
authors: Van Hecke
authors: Center Medical Genetics, Ghent University, Belgium.
authors: Pieter
authors: P
authors: Mestdagh
authors: Center Medical Genetics, Ghent University, Belgium.
authors: Steve
authors: S
authors: Lefever
authors: Inflammation Research Center, Flanders Institute of Biotechnology (VIB), Ghent, Belgium.|Department of Biomedical Molecular Biology Ghent University, Ghent, Belgium.
authors: Yvan
authors: Y
authors: Saeys
authors: Inflammation Research Center, Flanders Institute of Biotechnology (VIB), Ghent, Belgium.|Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
authors: Pieter
authors: P
authors: De Bleser
authors: Center Medical Genetics, Ghent University, Belgium.
authors: Jo
authors: J
authors: Vandesompele
authors: Institute of Microbiology (IMUL), Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
authors: Angela
authors: A
authors: Ciuffi
authors: Department of Internal Medicine, HIV Cure Research Centre, Ghent University, Ghent, Belgium.
authors: Linos
authors: L
authors: Vandekerckhove
authors: Department of Internal Medicine, HIV Cure Research Centre, Ghent University, Ghent, Belgium.|Department of Morphology, Ghent University, Belgium.
authors: Ward
authors: W
authors: De Spiegelaere
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger