Alteration in gene expression of HUVECs infected by HTNV
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ABSTRACT: Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon stimulate genes (ISGs) play important roles in viral infection. However, the role of ISGs in HTNV infection is unclear. In this study, we observed the alteration of gene expression in HUVECs infected with HTNV compared with mock infected control and found considerable changes in mRNA and lncRNA profiles.
Project description:Hemorrhagic Fever with Renal Syndrome (HFRS) is a regional infectious disease of epidemic potential caused by the Hantaan Virus (HTNV).The studies on immunological responses during HTNV infection have continuously been performed. During HTNV infection, lymphocytes are following a tightly controlled genetic programme.The pathological changes of PBMCs also occured during HTNV infection. We used single cell RNA sequencing to detail the cellular components and gene expression profiles of PBMCs underlying HTNV infection.
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.
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.
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.
Project description:Hantavirus causes two kinds of acute diseases; hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), and it is still a major health concern due to high mortality and lack of effective treatment. Interferon is only effective to inhibit hantavirus infection at a very early stage. Several interferon-stimulated genes (ISGs) have been indicated to inhibit hantavirus infection. The cholesterol 25-hydroxylase (CH25H) has been indicated as an ISG, which encodes an enzyme that catalyzes the production of 25-hydroxycholesterol (25HC). 25HC plays an important role in regulating cholesterol biosynthesis and inhibits multiple enveloped virus infections. Here, we showed that Hantaan virus (HTNV), the prototype hantavirus, induces CH25H in infected cells. Overexpression of CH25H and treatment of its enzymatic product 25HC both inhibit HTNV infection, possibly through lowering 3-hydroxy-3-methyl-glutaryl coenzyme A reductase regulation (HMG-CoA reductase, HMGCR) that inhibit cholesterol synthesis. Additionally, cholesterol lowering drugs, HMGCR-targeting statins process potent hantavirus inhibition effects. Taken together, our results indicate that the 25HC and statins were potential antivirals against hantavirus infection.
Project description:Hemorrhagic fever with renal syndrome (HFRS) caused by hantaan virus (HTNV) infection displays variable clinical signs. Humoral responses are important players against HTNV infections, however, this process is poorly understood. Herein, we investigated the phenotype, temporal dynamics, and characteristics of B-cell receptor repertoire (BCR) in a patient cohort with HFRS. The serological profile was characterized by low expression level of NP-specific antibody in severe cases. Importantly, B-cell subsets were activated and proliferated within the first two weeks of symptom onset, and the moderate cases reacted more rapidly. BCR analysis in the recovery phase revealed immunoglobulin gene diversity had dramatical rise and progressed more significant in the moderate group. The transcription of gene sets related to B-cell was lower, but the inflammatory sets were over-activated in severe cases. These data suggested the clinical signs and diseases recovery in HFRS patients were benefitted from rapid and efficacious humoral responses.
Project description:The murine bone marrow-derived macrophages (mBMDMs) were infected with Hantaan viruses (HTNV) with an MOI of 1, or mock-infected with Co60-inactivated HTNV. The mBMDM RNAs were extracted for RNA sequencing (RNA-seq) at 0 (mock-infected), 12, 24, and 36 hours post-infection (hpi). Each group contained three repeats (mBMDM from three different C57/6L mice). The data of 0 hpi group (labeled as A) were shown as A1, A2 and A3.The data of 12 hpi group (labeled as B) were shown as B1, B2 and B3. The data of 24 hpi group (labeled as C) were shown as C1, C2 and C3. The data of 36 hpi group (labeled as D) were shown as D1, D2 and D3.
Project description:Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome (PUUV-HFRS) is characterized by significant neutrophil activation. Neutrophils, the most abundant immune cells in circulation, are equipped to respond rapidly to infections and exhibit a notable heterogeneity. This study aims to identify and characterize different neutrophil subsets in the circulation of PUUV-HFRS patients, focusing on low-density granulocytes (LDGs) and normal density polymorphonuclear cells (PMNs). The study finds that PMNs show activation of antiviral pathways, while circulating LDGs increase following acute PUUV-HFRS. Additionally, PUUV-associated LDGs, primarily immature, likely reflect increased bone marrow neutrophil production. Notably, the frequency of LDGs and a "left shift" in blood are associated with the extent of thrombocytopenia, a hallmark of severe HFRS, suggesting a role for maturing neutrophils in disease pathogenesis. Unlike COVID-19 associated LDGs, PUUV LDGs did not exhibit significant immunosuppressive ability, indicating inherent biological differences in LDG responses based on the causative virus or infection kinetics. RNA sequencing was performed on neutrophils isolated from four cohorts: healthy control PMNs, PUUV-infected PMNs, PUUV-infected CD16- LDGs, and PUUV-infected CD16+ LDGs. The RNA sequencing and subsequent bioinformatics analysis were conducted by the Biomedicum Functional Genomics Unit at the Helsinki Institute of Life Science and Biocenter Finland at the University of Helsinki.
Project description:We report RNAseq analysis of control, calu3, astrocytes and cardiomyocytes cells under uninfected (mock) and Andes virus (ANDV), Sin Nombre virus (SNV), Hantaan virus (HTNV) infected and drug (synthetic 6AZA and Favipiravir, herbal Silymarin and Urolithin B) treated conditions
Project description:Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). While the mechanisms that lead to vascular permeability are unknown, the endothelium plays a central role in regulating fluid and cellular efflux from capillaries. Thus, dysregulation of endothelial cells functions by dengue virus infection may contribute to pathogenesis and severe disease. We used microarrays to investigate the effect of dengue virus infection on gene expression within primary human endothelial cells at various times post infection and identified numerous upregulated antiviral and immune response genes. Early passage primary endothelial cells (HUVECs) were mock infected (no virus) or infected with dengue virus and total RNA collected at 3 timepoints: 12, 24, and 48 hours post infection. Multiple timepoints were analyzed to identify changes in gene expression levels over time. Gene expression from both mock infected and dengue virus infected endothelial cells was evaluated to determine fold induction at each timepoint.