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Comprehensive Bioinformatics Analysis of the Immune Mechanism of Dendritic Cells Against Measles Virus.

ABSTRACT: BACKGROUND The purpose of this study was to explore the immune mechanism of dendritic cells (DCs) against measles virus (MV), and to identify potential biomarkers to improve measles prevention and treatment. MATERIAL AND METHODS The gene expression profile of GSE980, which comprised 10 DC samples from human blood infected with MV (RNA was isolated at 3, 6, 12, and 24 h post-infection) and 4 normal DC control samples, was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the MV-infected DC samples and the control samples were screened using Genevestigator software. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed using GenCLip 2.0 and STRING 10.5 software. The protein-protein interaction (PPI) network was established using Cytoscape 3.4.0. RESULTS The gene expression profiles of MV-infected DCs were obviously changed. Twenty-six common DEGs (0.9%, MV-infected DCs vs. normal DCs) were identified at 4 different time points, including 14 down-regulated and 12 up-regulated genes (P=0.001). GO analysis showed that DEGs were significantly enriched in defense response to virus, type I interferon signaling pathway, et al. ISG15 and CXCL10 were the key genes in the PPI network of the DEGs, and may interact directly with the type I interferon signaling and defense response to virus signaling. CONCLUSIONS The DEGs increased gradually with the duration of MV infection. The type I interferon signaling pathway and the defense response to viral processes can be activated against MV by ISG15 and CXCL10 in DCs. These may provide novel targets for the treatment of MV.

SUBMITTER: Jia L

PROVIDER: S-EPMC6367888 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Comprehensive Bioinformatics Analysis of the Immune Mechanism of Dendritic Cells Against Measles Virus.

Jia Lili L Zhang Rongqiang R

Medical science monitor : international medical journal of experimental and clinical research 20190201

BACKGROUND The purpose of this study was to explore the immune mechanism of dendritic cells (DCs) against measles virus (MV), and to identify potential biomarkers to improve measles prevention and treatment. MATERIAL AND METHODS The gene expression profile of GSE980, which comprised 10 DC samples from human blood infected with MV (RNA was isolated at 3, 6, 12, and 24 h post-infection) and 4 normal DC control samples, was obtained from the Gene Expression Omnibus database. Differentially expresse ...[more]

PMID: 30705250

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Project description:Although live-attenuated measles virus (MV) vaccines have been used successfully for over 50 years, the target cells that sustain virus replication in vivo are still unknown. We generated a reverse genetics system for the live-attenuated MV vaccine strain Edmonston-Zagreb (EZ), allowing recovery of recombinant (r)MV(EZ). Three recombinant viruses were generated that contained the open reading frame encoding enhanced green fluorescent protein (EGFP) within an additional transcriptional unit (ATU) at various positions within the genome. rMV(EZ)EGFP(1), rMV(EZ)EGFP(3), and rMV(EZ)EGFP(6) contained the ATU upstream of the N gene, following the P gene, and following the H gene, respectively. The viruses were compared in vitro by growth curves, which indicated that rMV(EZ)EGFP(1) was overattenuated. Intratracheal infection of cynomolgus macaques with these recombinant viruses revealed differences in immunogenicity. rMV(EZ)EGFP(1) and rMV(EZ)EGFP(6) did not induce satisfactory serum antibody responses, whereas both in vitro and in vivo rMV(EZ)EGFP(3) was functionally equivalent to the commercial MV(EZ)-containing vaccine. Intramuscular vaccination of macaques with rMV(EZ)EGFP(3) resulted in the identification of EGFP(+) cells in the muscle at days 3, 5, and 7 postvaccination. Phenotypic characterization of these cells demonstrated that muscle cells were not infected and that dendritic cells and macrophages were the predominant target cells of live-attenuated MV.Even though MV strain Edmonston-Zagreb has long been used as a live-attenuated vaccine (LAV) to protect against measles, nothing is known about the primary cells in which the virus replicates in vivo. This is vital information given the push to move toward needle-free routes of vaccination, since vaccine virus replication is essential for vaccination efficacy. We have generated a number of recombinant MV strains expressing enhanced green fluorescent protein. The virus that best mimicked the nonrecombinant vaccine virus was formulated according to protocols for production of commercial vaccine virus batches, and was subsequently used to assess viral tropism in nonhuman primates. The virus primarily replicated in professional antigen-presenting cells, which may explain why this LAV is so immunogenic and efficacious.

Dataset Information

Comprehensive Bioinformatics Analysis of the Immune Mechanism of Dendritic Cells Against Measles Virus.

Publications

Comprehensive Bioinformatics Analysis of the Immune Mechanism of Dendritic Cells Against Measles Virus.

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