Interferon-Mediated Long Non-Coding RNA Response in Macrophages in the Context of HIV

Schynkel, Tinus; Szaniawski, Matthew A.; Spivak, Adam M.; Bosque, Alberto; Planelles, Vicente; Vandekerckhove, Linos; Trypsteen, Wim

doi:10.3390/ijms21207741

Cited by 12 publications

(7 citation statements)

References 51 publications

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“…In our analysis, it was observed that several deregulated lncRNA, as well as many PCG, could be regulated by IFN treatments. Expressions of several lncRNAs are shown to be modulated by treatment with IFNs [8,130,131]. Some of the deregulated lncRNA and PCG thus could be regulated in response to abnormal IFN in COVID-19.…”

Section: Involvement Of Deregulated Lncrna In the Pathogenesis Of Cov...mentioning

confidence: 99%

Co-Regulation of Protein Coding Genes by Transcription Factor and Long Non-Coding RNA in SARS-CoV-2 Infected Cells: An In Silico Analysis

Saha

Laha

Chatterjee

et al. 2021

ncRNA

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Altered expression of protein coding gene (PCG) and long non-coding RNA (lncRNA) have been identified in SARS-CoV-2 infected cells and tissues from COVID-19 patients. The functional role and mechanism (s) of transcriptional regulation of deregulated genes in COVID-19 remain largely unknown. In the present communication, reanalyzing publicly available gene expression data, we observed that 66 lncRNA and 5491 PCG were deregulated in more than one experimental condition. Combining our earlier published results and using different publicly available resources, it was observed that 72 deregulated lncRNA interacted with 3228 genes/proteins. Many targets of deregulated lncRNA could also interact with SARS-CoV-2 coded proteins, modulated by IFN treatment and identified in CRISPR screening to modulate SARS-CoV-2 infection. The majority of the deregulated lncRNA and PCG were targets of at least one of the transcription factors (TFs), interferon responsive factors (IRFs), signal transducer, and activator of transcription (STATs), NFκB, MYC, and RELA/p65. Deregulated 1069 PCG was joint targets of lncRNA and TF. These joint targets are significantly enriched with pathways relevant for SARS-CoV-2 infection indicating that joint regulation of PCG could be one of the mechanisms for deregulation. Over all this manuscript showed possible involvement of lncRNA and mechanisms of deregulation of PCG in the pathogenesis of COVID-19.

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Section: Involvement Of Deregulated Lncrna In the Pathogenesis Of Cov...mentioning

confidence: 99%

Co-Regulation of Protein Coding Genes by Transcription Factor and Long Non-Coding RNA in SARS-CoV-2 Infected Cells: An In Silico Analysis

Saha

Laha

Chatterjee

et al. 2021

ncRNA

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“…Expression of lncRNA EGOT, NEAT1, BISPR/LncBST2, LINC01191/VIN/lnc-ACTR3, ISR (IFN-stimulated lncRNA) 2 and ISR8, LOC100506319/LINC01988/LncRNA-PAAN, LOC102637961/lncRNA-ACOD1, MIR155HG, TSPOAP1-AS1, PSMB8-AS1, PSORS1C3, IVRPIE was increased and expression of NRAV/DYNLL1AS1 was decreased in IAV infected cells 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 . In HIV infected cells expression of ISR2, NEAT1, GOMAFU/MIAT, LUST/RBM5-AS1, BIC/MIR155HG, MALAT1, NRIR/lncCMPK2, MIR3945HG, FIRRE, LINC02574, LINC01426 is increased while expression of NRON, PANDAR/PANDA, CDKN2B-AS1/ANRIL DD3/PCA, DANCR, CMPD/LINC01152, NCRMS/RMST, GAS5, LINC00173, lincRNA-p21/TP53COR1 and SAF/FAS-AS1 is decreased 29 , 30 , 31 . Increased expression of NEAT1, MAMDC2-AS1, PRINS, ISR2 and LOC102637961/lncRNA-ACOD1 is observed in HSV infected cells 24 , 27 , 32 , 33 , 34 .…”

Section: Introductionmentioning

confidence: 99%

In silico analysis of altered expression of long non-coding RNA in SARS-CoV-2 infected cells and their possible regulation by STAT1, STAT3 and interferon regulatory factors

Laha

Saha

Dutta

et al. 2021

Heliyon

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Altered expression of long noncoding RNA (lncRNA), longer than 200 nucleotides without potential for coding protein, has been observed in diverse human diseases including viral diseases. It is largely unknown whether lncRNA would deregulate in SARS-CoV-2 infection, causing ongoing pandemic COVID-19. To identify, if lncRNA was deregulated in SARS-CoV-2 infected cells, we analyzed in silico the data in GSE147507. It was revealed that expression of 20 lncRNA like MALAT1, NEAT1 was increased and 4 lncRNA like PART1, TP53TG1 was decreased in at least two independent cell lines infected with SARS-CoV-2. Expression of NEAT1 was also increased in lungs tissue of COVID-19 patients. The deregulated lncRNA could interact with more than 2800 genes/proteins and 422 microRNAs as revealed from the database that catalogs experimentally determined interactions. Analysis with the interacting gene/protein partners of deregulated lncRNAs revealed that these genes/proteins were associated with many pathways related to viral infection, inflammation and immune functions. To find out whether these lncRNAs could be regulated by STATs and interferon regulatory factors (IRFs), we used ChIPBase v2.0 that catalogs experimentally determined binding from ChIP-seq data. It was revealed that any one of the transcription factors IRF1, IRF4, STAT1, STAT3 and STAT5A had experimentally determined binding at regions within -5kb to +1kb of the deregulated lncRNAs in at least 2 independent cell lines/conditions. Our analysis revealed that several lncRNAs could be regulated by IRF1, IRF4 STAT1 and STAT3 in response to SARS-CoV-2 infection and lncRNAs might be involved in antiviral response. However, these in silico observations are necessary to be validated experimentally.

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“…In the last two decades, with the introduction of large sequencing projects and a multitude of functional studies, lncRNAs have been recognized as key players in regulatory pathways and diseases, including HIV-1 infection [ 4 , 5 , 6 , 20 ]. Although ample in vitro research has led to substantial progress in understanding the role of lncRNAs during HIV-1 infection, little is known about their expression in vivo.…”

Section: Discussionmentioning

confidence: 99%

Evaluating lncRNA Expression Patterns during HIV-1 Treatment Interruption

Schynkel

Snippenberg

Hecke

et al. 2023

IJMS

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Lately, the interest in long non-coding RNAs (lncRNAs) as potential drug targets and predictive markers in the context of HIV-1 has peaked, but their in vivo expression and regulation remains largely unexplored. Therefore, the present study examined lncRNA expression patterns during a clinical antiretroviral treatment interruption (ATI) trial. Peripheral blood mononuclear cells were isolated from ten patients at four timepoints: prior to ATI, 7–15 days after stop, at viral rebound and 3 months post antiretroviral therapy re-initiation. RNA was extracted and RT-qPCR on five known HIV-1-related lncRNAs (HEAL, MALAT1, NEAT1, GAS5 and NRON) was performed and correlated with HIV-1 and host marker expression. All lncRNAs correlated stronger with interferon stimulated genes (ISGs) than with HIV-1 reservoir and replication markers. However, one lncRNA, HEAL, showed significant upregulation at viral rebound during ATI compared to baseline and re-initiation of therapy (p = 0.0010 and p = 0.0094, respectively), following a similar viral-load-driven expression pattern to ISGs. In vitro knockdown of HEAL caused a significant reduction in HIV-1 infection levels, validating HEAL’s importance for HIV-1 replication. We conclude that the HIV-1-promoting lncRNA HEAL is upregulated at viral rebound during ATI, most likely induced by viral cues.

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Interferon-Mediated Long Non-Coding RNA Response in Macrophages in the Context of HIV

Cited by 12 publications

References 51 publications

Co-Regulation of Protein Coding Genes by Transcription Factor and Long Non-Coding RNA in SARS-CoV-2 Infected Cells: An In Silico Analysis

Co-Regulation of Protein Coding Genes by Transcription Factor and Long Non-Coding RNA in SARS-CoV-2 Infected Cells: An In Silico Analysis

In silico analysis of altered expression of long non-coding RNA in SARS-CoV-2 infected cells and their possible regulation by STAT1, STAT3 and interferon regulatory factors

Evaluating lncRNA Expression Patterns during HIV-1 Treatment Interruption

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