ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/037/SRR11431737/SRR11431737.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/026/SRR11431726/SRR11431726.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/032/SRR11431732/SRR11431732.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/043/SRR11431743/SRR11431743.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/020/SRR11431720/SRR11431720.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/031/SRR11431731/SRR11431731.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/025/SRR11431725/SRR11431725.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/042/SRR11431742/SRR11431742.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/021/SRR11431721/SRR11431721.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/036/SRR11431736/SRR11431736.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/019/SRR11431719/SRR11431719.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/033/SRR11431733/SRR11431733.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/022/SRR11431722/SRR11431722.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/030/SRR11431730/SRR11431730.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/044/SRR11431744/SRR11431744.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/018/SRR11431718/SRR11431718.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/041/SRR11431741/SRR11431741.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/029/SRR11431729/SRR11431729.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/028/SRR11431728/SRR11431728.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/034/SRR11431734/SRR11431734.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/040/SRR11431740/SRR11431740.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/023/SRR11431723/SRR11431723.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/038/SRR11431738/SRR11431738.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/027/SRR11431727/SRR11431727.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/039/SRR11431739/SRR11431739.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/035/SRR11431735/SRR11431735.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR114/024/SRR11431724/SRR11431724.fastq.gzprimary200OKGenomicsMRC-University of Glasgowhttps://www.ebi.ac.uk/ena/browser/view/PRJNA615795xref:EuropePMC:PMC7387431Long non-coding RNAs (lncRNAs) are transcripts of more than 200 nucleotides that are not translated into functional proteins. Cellular lncRNAs have been shown to act as regulators by interacting with target nucleic acids or proteins and modulating their activities. We investigated the role of RNA1.2, which is one of four major lncRNAs expressed by human cytomegalovirus (HCMV), by comparing the properties of parental virus in vitro with those of deletion mutants lacking either most of the RNA1.2 gene or only the TATA element of the promoter. In comparison with parental virus, these mutants exhibited no growth defects and minimal differences in viral gene expression in human fibroblasts. In contrast, 76 cellular genes were consistently up- or down-regulated by the mutants at both the RNA and protein levels at 72 hours after infection. Differential expression of the gene most highly upregulated by the mutants (Tumor protein p63-regulated gene 1-like protein TPRG1L) was confirmed at both levels by RT-PCR and immunoblotting. Consistent with the known ability of TPRG1L to upregulate IL-6 expression via NF- kappaB stimulation, RNA1.2 mutant-infected fibroblasts were observed to upregulate IL-6 in addition to TPRG1L. Comparable surface expression of TNF receptors and responsiveness to TNF-alpha in cells infected by the parental and mutant viruses indicated that activation of signaling by TNF-alpha is not involved in upregulation of IL-6 by the mutants. In contrast, inhibition of NF-kappaB activity and knockdown of TPRG1L expression reduced the extracellular release of IL-6 by RNA1.2 mutant-infected cells, thus demonstrating that upregulation of TPRG1L activates NF-kappaB. The levels of CCL2 and CXCL1 transcripts were also increased in RNA1.2 mutant-infected cells, further demonstrating the presence of active NF- kappaB signalling. These results suggest that RNA1.2 plays a role in manipulating intrinsic NF- kappaB-dependent cytokine and chemokine release during HCMV infection, thereby impacting downstream immune responses.ENADifferentiation-Inducing Protein, Myeloid Differentiation-Inducing Protein, B-Cell Stimulatory Factor-2, Disease, CDF, MGI-2, Myeloid, Il-6, CYTOMEGALIC INCLUSION DIS, B-cell hybridoma growth factor, Cytomegalic Inclusion, Hepatocyte-Stimulating Factor, CMV infection, B-Cell, B Cell Stimulatory Factor-2, beta-2, Myeloid Differentiation Inducing Protein, B-Cell Differentiation Factor, HSF, CYTOMEGALOVIRAL DISEASE, Inclusion Diseases, unspecified (disorder), B-cell stimulatory factor 2, B Cell, BSF2, Interferon beta 2, B Cell Stimulatory Factor 2, unspecified, HGF, Cytomegalovirus Infections, CMV - Cytomegalovirus infection, SALIVARY GLAND VIRUS DIS, Cytomegalovirus infectious disease, IFN-beta-2, IL-6, Hepatocyte Stimulating Factor, Diseases, Infection, Interferon beta-2, BSF-2, Hybridoma growth factor, NOS, Growth Factor, Differentiation Factor-2, CTL differentiation factor, HCMV infection, cytomegalovirus infection, Cytomegaloviral infection, CYTOMEGALOVIRUS INFECT, INFECT CYTOMEGALOVIRUS, B-Cell Differentiation Factor-2, IFN-beta 2, Differentiation Factor 2, HCMV, Cytomegalovirus infection, Differentiation Factor, Infections, Cytomagalovirus infection, Cytomegalic, Hybridoma Growth Factor, Cytomegaloviral disease, Interleukin 6, Interleukin HP-1, Cytomegalovirus Infection, B Cell., Salivary gland virus disease, Cytomegalic Inclusion Diseases, [X]Cytomegaloviral disease, Plasmacytoma, Human Herpesvirus 5, Cytomegalovirus, B Cell Differentiation Factor 2, IFNB2, interleukin-6 receptor ligand, B Cell Differentiation Factor, Hybridoma, Plasmacytoma Growth Factor, B-Cell Stimulatory Factor 2, Cytomegalic inclusion disease, IL6, INCLUSION DIS, Cytomegalovirus infection (disorder), Interferon, Inclusion Disease, Disease due to CytomegalovirusfalseHCMV lncRNA1.2 suppresses IL-62023-05-172020-07-10PRJNA615795