Differential Tropisms of Old and New World Hantaviruses Influence Virulence and Developing Host-Directed Antiviral Candidates
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE232641 | GEO | 2024/05/16
REPOSITORIES: GEO
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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.
2021-04-28 | GSE161354 | GEO
Project description: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.
2017-12-31 | GSE86282 | GEO
Project description:Hantaan virus is a dangerous human pathogen whose segmented negative-stranded RNA genome is replicated and transcribed by a virally-encoded multi-functional polymerase. To describe the complete cryo-electron microscopy structure of Hantaan virus polymerase in several oligomeric forms, a full-length wild-type (WT) HTNV-L construct comprising an N-terminal his-tag was expressed in Hi5 insect cells and subsequently purified. Through a combination of size-exclusion chromatography and mass photometry analysis, the presence of distinct HTNV-L oligomers was observed. In buffers containing 250mM NaCl, several species were automatically detected including monomers (53%), dimers (17%), higher molecular weight oligomers up to hexamers (2%) and an unidentified 150kDa protein (18%). To characterize the proteins present in the 150kDa band, a bottom-up mass spectrometry (MS)-based proteomic analysis was performed. For this, proteins present in the 150 kDa band were in-gel digested with trypsin before analysis by nano liquid chromatography coupled to MS/MS. Obtained result revealed that the most abundant protein in this band was HTNV-L. The identified peptides were covering the entire HTNV-L sequence, suggesting that the 150kDa band may contain different cleaved forms of HTNV-L co-migrating in this particular SDS-PAGE gel band.
2024-02-07 | PXD049232 | Pride
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.
2020-04-06 | GSE133319 | GEO
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.
2020-04-06 | GSE133751 | GEO
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.
2020-04-06 | GSE133634 | GEO
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.
2022-02-05 | E-MTAB-11353 | biostudies-arrayexpress
Project description:Hantavirus infection has become a public health concern worldwide due to its ability to cause severe diseases in humans. The virulence of Hantavirus is determined by their ability to restrain host innate immune responses, such as type Ⅰ interferon (IFN-Ⅰ) response. Here, we demonstrated that Hantaan virus (HTNV), a prevalent pathogen that causes hemorrhagic fever with renal syndrome in China, can inhibit host IFN-Ⅰ production by manipulating the retinoic acid-induced gene I (RIG-I)-like receptor (RLRs) pathways. In brief, we performed the transcriptome analysis to identify the host factors regulated by nucleocapsid protein (NP) and glycoprotein (Gc) of HTNV, which showed that multiple cellular biological pathways were regulated by NP and Gc, including interferon signaling pathways, neuron differentiation, and response to mechanical stimulus. Further analysis demonstrated that HTNV NP and Gc proteins inhibited IFN-Ⅰ response by targeting MAVS upstream molecules, such as RIG-I and MDA-5. Mechanistically, NP and Gc proteins suppressed RIG-I and MDA-5-induced IFN-Ⅰ production by targeting TRIM25, rather than directly actin on RIG-I and MDA-5. Taken together, our study revealed a cross-talk between HTNV NP or Gc proteins and host innate immune response, which is helpful in the understanding of virus-host interaction in general.
2025-04-30 | GSE231456 | GEO
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.
2024-06-27 | GSE252127 | GEO
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.
2020-09-30 | GSE158712 | GEO