Project description:There is increasing evidence showing that aberrant expressions of circRNAs are implicated in various physiological or pathological processes. Yet, their roles in antiviral innate immunity remain unknown. To reveal the implications of circRNAs in antiviral innate immunity, we used Human circRNA Array v2.0 microarrays to measure the expression profiles of circRNAs in HEK293 cells infected with or without Sendai virus(SeV). We found 82 up-regulated and 20 down-regulated circRNAs(fold change >2; P <0.05) in HEK293 cells after SeV infection. Upregulation of circRNA hsa_circ_0006916 was established using Real-time quantitative PCR. These results showed abrrant expression profiles of circRNAs in HEK293 cells after SeV infection and revealed their potential roles in antiviral innate immunity.
Project description:To analyze the effect of Transmissible gastroenteritis virus (TGEV) infection on expression profile of circular RNAs (circRNAs) in pig renal epithelial cells (PK-15), we decided to sequence the circRNAs transcriptome of control and TGEV-infected PK-15 cells based on the Illumina HiSeq 4000 platform. The source genes of the differentially expressed circRNAs were subjected to GO function and KEGG pathway enrichment analysis. Meanwhile, we built a regulatory network of DE circRNAs and predicted multiple circRNA-miRNA-mRNA regulatory axes about innate immunity and the pathogenesis of TGEV. In this study, transcriptome sequencing results revealed that a total of 1029 novel circRNAs were identified in the control and TGEV- infected PK -15 cells. In TGEV-infected PK-15 cells, the expression levels of 70 circRNAs were significantly up-regulated and 58 circRNAs were significantly down-regulated compared to control PK-15 cells. GO functional analysis of the source genes of differentially expressed circRNAs indicated that the differentially expressed circRNAs source genes in TGEV-infected PK-15 cells were mainly enriched in the intracellular part, intracellular membrane-bounded organelle and nucleus and cellular macromolecule metabolic process, nucleobase-containing compound metabolic process, nitrogen compound metabolic process, and regulation of cellular metabolic process and heterocyclic compound binding, organic cyclic compound binding and nucleic acid binding.The results of KEGG pathway enrichment analysis showed that the significantly differentially expressed circRNAs source genes in the TGEV-infected PK -15 cells were mainly enriched in the regulation of actin cytoskeleton, influenza A, hepatitis C and cAMP signaling pathway. circRNA-miRNA-mRNA interaction networks demonstrated that circRNAs regulated innate immunity and transmembrane ion transport.
Project description:The aim of this study was to identify differential gene and protein expression associated with GBV-C that may be of importance in reduction of HCV-related liver disease. GB virus C (GBV-C) infection leads to improved outcomes in human immunodeficiency virus (HIV) infection. Furthermore, GBV-C has been shown to reduce hepatitis C virus (HCV)-related liver disease in HCV/HIV co-infection.
Project description:The aim of this study was to identify differential gene and protein expression associated with GBV-C that may be of importance in reduction of HCV-related liver disease. GB virus C (GBV-C) infection leads to improved outcomes in human immunodeficiency virus (HIV) infection. Furthermore, GBV-C has been shown to reduce hepatitis C virus (HCV)-related liver disease in HCV/HIV co-infection. We aimed to identify differential gene expression associated with GBV-C in HCV/HIV co-infection by comparing RNA expression from liver biopsies of HCV/HIV co-infected patients with and without GBV-C infection. Liver biopsies were obtained from 10 Patients with HCV/HIV co-infection; 4 of these patients were positive for GBV-C infection and 6 were negative for GBV-C infection. The tissue was stored in RNAlater and RNA was extracted for hybridisation to Affymetrix Human Genome U133 plus 2.0 microarrays at the University of Texas Medical Branch Molecular Genomics Core Laboratory. The data was analysed for genes differentially expressed between GBV-C positive and negative patients using Partek Genomics suite and applying a custom CDF file (Hs133P_Hs_UG_8), available from Molecular and Behavioural Neuroscience Institute, University of Michigan.
Project description:Our study's objective was to determine circRNA expression alterations following in vivo influenza virus infection. We challenged C57BL/6 for 48 hours with IAV-PR8. Lung samples were obtained, RNA-Seq was utilized, and the circRNAs transcriptome data was compared to the control.
Project description:We previously reported widespread differential expression of long non-protein-coding RNAs (ncRNAs) in response to virus infection. Here, we expanded the study through small RNA transcriptome sequencing analysis of the host response to both severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza virus infections across four founder mouse strains of the Collaborative Cross, a recombinant inbred mouse resource for mapping complex traits. We observed differential expression of over 200 small RNAs of diverse classes during infection. A majority of identified microRNAs (miRNAs) showed divergent changes in expression across mouse strains with respect to SARS-CoV and influenza virus infections and responded differently to a highly pathogenic reconstructed 1918 virus compared to a minimally pathogenic seasonal influenza virus isolate. Novel insights into miRNA expression changes, including the association with pathogenic outcomes and large differences between in vivo and in vitro experimental systems, were further elucidated by a survey of selected miRNAs across diverse virus infections. The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. These findings represent the first integrated sequencing analysis of the response of host small RNAs to virus infection and show that small RNAs are an integrated component of complex networks involved in regulating the host response to infection. IMPORTANCE: Most studies examining the host transcriptional response to infection focus only on protein-coding genes. However, mammalian genomes transcribe many short and long non-protein-coding RNAs (ncRNAs). With the advent of deepsequencing technologies, systematic transcriptome analysis of the host response, including analysis of ncRNAs of different sizes, is now possible. Using this approach, we recently discovered widespread differential expression of host long (>200 nucleotide[nt]) ncRNAs in response to virus infection. Here, the samples described in the previous report were again used, but we sequenced another fraction of the transcriptome to study very short (about 20 to 30 nt) ncRNAs. We demonstrated that virus infection also altered expression of many short ncRNAs of diverse classes. Putting the results of the two studies together, we show that small RNAs may also play an important role in regulating the host response to virus infection.
Project description:Background: Of Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), 85%-90% of cases develop from liver cirrhosis, and circular RNAs (circRNAs) have important roles in this process; however, differences in serum circRNA expression profiles between patients with HBV-related cirrhosis and those with HCC have not been studied. Methods: Serum RNA was extracted from patients with HCC and cirrhosis (n = 5 per group) and used for microarray analysis of circRNA expression profiles. Bioinformatics analyses, including clustering, differential expression, and construction of a ceRNA network, were performed. Quantitative real-time reverse transcription PCR validation analysis was conducted using samples from patients with HBV-related cirrhosis (n = 88) and HCC (n = 73). Further, statistical analyses were used to analyze the potential function and value of selected circRNAs with expression differing between the HBV-related cirrhosis and HCC groups. Results: Cluster analysis revealed 8 up-regulated and 80 down-regulated circRNAs. Further, qRT-PCR analysis showed that circRNA_0000367 expression was consistent with that detected by microarray experiments, with significantly lower levels in patients with HBV-related HCC than those with HBV-related cirrhosis. CircRNA_0000367 expression levels were also significantly lower in patients with drug-resistant HBV and those with HBV-related cirrhosis with Model for End-Stage Liver Disease score < 10. Further, circRNA_00000367 expression levels were lower in patients with HBV-related cirrhosis who progressed to HCC. Analysis of the lncRNA-miRNA-mRNA ceRNA network identified 39 miRNAs and 24 mRNAs involved in circRNA_00000367 networks; these target genes were involved in various biological processes and signaling pathways. Conclusion: Serum cicrRNA_0000367 is a potential HCC biomarker in patients with HBV-related cirrhosis, where down-regulation of cicrRNA_0000367 in HBV-related cirrhosis may be associated with progression to HCC.
Project description:To investigate the changes in circRNAs expression after SVA infection in PK-15 cells, we established a model of SVA-infected PK-15 cells.
Project description:Hantaan virus (HTNV), the prevalent prototype of the hantavirus in Asia, causes hemorrhagic fever with renal syndrome (HFRS) with high mortality in human being. However, the pathogenesis of HTNV infection remains elusive. Accumulating evidences indicate that non-coding RNAs (ncRNAs), including long non-coding RNA (lncRNA), circular RNA (circRNA) and microRNA (miRNA) play crucial roles in the progression of virus infection. Here, we identified differential lncRNA/miRNA/circRNA and mRNA expression profiles of HTNV-infected human umbilical vein endothelial cells (HUVECs) compared with mock-infected HUVECs by whole transcriptome sequencing. Subsequently, comprehensive bioinformatics analyses established miRNA-mRNA co-expression, protein-protein interaction and competing endogenous RNA (ceRNA) networks in miRNA-lncRNA-circRNA-mRNA regulatory axis. The trans or cis regulatory roles of identified RNAs on HTNV infection were ascertained by RNA interference and key ceRNA relationships were verified by dual-luciferase reporter experiments. Moreover, gene ontology (GO) enrichment analysis showed that dysregulated RNAs were mostly related to antiviral innate immune response. In conclusion, our findings firstly revealed that circRNAs and ceRNA network were involved in regulating HTNV infection, and also confirmed several key lncRNAs and miRNAs which had vital effects on HTNV infection. The identification and characterization of RNAs provide the new insights on ceRNA networks in HTNV-host interactions, which lays the foundation for future research of the potential roles of ncRNAs in the pathogenesis of HFRS.