Analyses of viruses from vaccine induced rabies cases and corresponding vaccine batches
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PROVIDER: PRJEB35810 | ENA |
REPOSITORIES: ENA
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Project description:In-depth genome analyses of viruses from vaccine-derived rabies cases and corresponding live-attenuated oral rabies vaccines
| PRJEB21530 | ENA
Project description:Rabies is an ancient infectious disease but still lacking efficient therapeutic approach despite of vaccine. In this study, we have identified a novel cytoplasmic lncRNA, namely rabies virus related lncRNA 1(RVRL1), whose expression in neuronal cells is up-regulated upon the infection of the causative agent of rabies, the neurotropic virus rabies virus (RABV). RVRL1 effectively inhibits RABV infection both in neuronal cells and in a mouse model. RVRL1 binds to EZH2 and disrupts the PRC2 complex, which is consistent with the inverse relationship between RVRL1 expression and the cellular H3K27me3 level. RVRL1 expression positively regulates the expression of PCP4L1 encoding a 10 kD peptide, which is shown to inhibit RABV replication. These findings highlight a novel mechanism for lncRNAs to upregulate the expression of antiviral genes, and define two potential anti-rabies reagents including an antiviral lncRNA and an antiviral peptide.
2020-09-08 | GSE107285 | GEO
Project description:Rabies is an ancient infectious disease but still lacking efficient therapeutic approach despite of vaccine. In this study, we have identified a novel cytoplasmic lncRNA, namely rabies virus related lncRNA 1(RVRL1), whose expression in neuronal cells is up-regulated upon the infection of the causative agent of rabies, the neurotropic virus rabies virus (RABV). RVRL1 effectively inhibits RABV infection both in neuronal cells and in a mouse model. RVRL1 binds to EZH2 and disrupts the PRC2 complex, which is consistent with the inverse relationship between RVRL1 expression and the cellular H3K27me3 level. RVRL1 expression positively regulates the expression of PCP4L1 encoding a 10 kD peptide, which is shown to inhibit RABV replication. These findings highlight a novel mechanism for lncRNAs to upregulate the expression of antiviral genes, and define two potential anti-rabies reagents including an antiviral lncRNA and an antiviral peptide.
2020-09-08 | GSE107277 | GEO
Project description:Viral vectors are essential tools for the study of neural circuits, with glycoprotein-deleted rabies viruses being widely used for monosynaptic retrograde tracing to map connectivity between specific cell types in the nervous system. However, the use of rabies virus is limited by the cytotoxicity and the inflammatory responses these viruses trigger. While components of the rabies virus genome contribute to its cytotoxic effects, the function of other neuronal and non-neuronal cells within the vicinity of the infected host neurons in either effecting or mitigating virally-induced tissue damage are still being elucidated. Here we analyzed 60,212 single-cell RNA profiles to assess both global and cell type-specific transcriptional responses in the mouse dorsal raphe nucleus following intracranial injection of glycoprotein-deleted rabies viruses and axonal infection of dorsal raphe serotonergic neurons. Gene pathway analyses revealed a down-regulation of genes involved in metabolic processes and neurotransmission following infection. We also identified several transcriptionally diverse leukocyte populations that infiltrate the brain and are distinct from resident immune cells. Cell type-specific patterns of cytokine expression showed that antiviral responses were likely orchestrated by Type I and Type II interferon signaling from microglia and infiltrating CD4+ T cells, respectively. Additionally, we uncovered transcriptionally distinct states of microglia along an activation trajectory that may serve different functions, which range from surveillance to antigen presentation and cytokine secretion. Intercellular interactions inferred from transcriptional data suggest that CD4+ T cells facilitate microglial state transitions during the inflammatory response. Our study uncovers the heterogeneity of immune cells mediating neuroinflammatory responses, and provides a critical evaluation of the compatibility between rabies-mediated connectivity mapping and single-cell transcriptional profiling. These findings provide additional insights into the distinct contributions of various cell types in mediating different facets of antiviral responses in the brain, and will facilitate the design of strategies to circumvent immune responses to improve the efficacy of viral gene delivery.
2020-01-17 | GSE136455 | GEO
Project description:It is well established that the pathogenicity and pathology of rabies virus (RABV) varies according to the variant, but the exact mechanism for this is still not completely known. In this study, the gene expression profile in brains of mice infected with virus isolated from a human case of dog rabies (V2) or vampire bat-acquired rabies (V3) were analyzed in experimental condition. In total, 138 array probes associated with 120 genes were differentially expressed between mice inoculated with V2 and the control mice at day 10 post-inoculation. A single probe corresponding to an unannotated gene was identified in V3 versus control mice. Gene ontology (GO) analysis revealed that all of the genes up-regulated in mice inoculated with V2 were involved in the biological process of immune defense against pathogens. Although both variants being considered pathogenic, inoculation in exactly same condition generated particular results regarding gene expression, more likely to differences in pathogenesis between dog and bat-related variants, already considered in other studies. This study was the first to demonstrate the global gene expression in experimental rabies infection due to V3 wild-type rabies virus, which reservoir is the vampire bat Desmodus rotundus, an important transmitter of rabies for humans and production animals in Latin America.
2022-02-28 | E-MTAB-11414 | biostudies-arrayexpress
Project description:Shigui Ruan. Modeling the transmission dynamics and control of rabies in China. Mathematical Biosciences 286 (2017).
Human rabies was first recorded in ancient China in about 556 BC and is still one of the major public-health problems in China. From 1950 to 2015, 130,494 human rabies cases were reported in Mainland China with an average of 1977 cases per year. It is estimated that 95% of these human rabies cases are due to dog bites. The purpose of this article is to provide a review about the models, results, and simulations that we have obtained recently on studying the transmission of rabies in China. We first construct a basic susceptible, exposed, infectious, and recovered (SEIR) type model for the spread of rabies virus among dogs and from dogs to humans and use the model to simulate the human rabies data in China from 1996 to 2010. Then we modify the basic model by including both domestic and stray dogs and apply the model to simulate the human rabies data from Guangdong Province, China. To study the seasonality of rabies, in Section 4 we further propose a SEIR model with periodic transmission rates and employ the model to simulate the monthly data of human rabies cases reported by the Chinese Ministry of Health from January 2004 to December 2010. To understand the spatial spread of rabies, in Section 5 we add diffusion to the dog population in the basic SEIR model to obtain a reaction-diffusion equation model and determine the minimum wave speed connecting the disease-free equilibrium to the endemic equilibrium. Finally, in order to investigate how the movement of dogs affects the geographically inter-provincial spread of rabies in Mainland China, in Section 6 we propose a multi-patch model to describe the transmission dynamics of rabies between dogs and humans and use the two-patch submodel to investigate the rabies virus clades lineages and to simulate the human rabies data from Guizhou and Guangxi, Hebei and Fujian, and Sichuan and Shaanxi, respectively. Some discussions are provided in Section 7.
2024-09-02 | BIOMD0000000726 | BioModels
Project description:Mandatory potency testing of Leptospira vaccine batches relies partially on in vivo procedures, requiring large numbers of laboratory animals. Cell-based assays could replace in vivo tests if biomarkers indicative of Leptospira vaccine potency are identified. We investigated innate immune responsiveness induced by inactivated L. interrogans serogroups Canicola and Icterohaemorrhagiae, and two bivalent, non-adjuvanted canine Leptospira vaccines containing the same serogroups. First, the transcriptome and proteome analysis of canine 030-D cells stimulated with Leptospira strains, and the corresponding vaccine revealed more than 900 DEGs and 23 DEPs in common to these three stimuli. Second, comparison of responses induced by this Leptospira vaccine and a vaccine from another manufacturer revealed a large overlap in DEGs and DEPs as well, suggesting potential to identify biomarkers of Leptospira vaccine activity. Because not many common DEPs were identified, we selected seven molecules from the identified DEGs, associated with pathways related to innate immunity, of which CXCL-10, IL-1β, SAA, and complement C3 showed increased secretion upon stimulation with both Leptospira vaccines. These molecules could be interesting targets for development of biomarker-based assays in the future. Additionally, this study contributes to the understanding of the mechanisms by which Leptospira vaccines induce innate immune responses in the dog.
2022-03-06 | PXD031875 | Pride
Project description:Cortical circuit tracing using modified rabies virus can identify input neurons making direct monosynaptic connections onto neurons of interest. However, challenges remain in our ability to establish the cell type identity of rabies-labeled input neurons. While transcriptomics may offer an avenue to characterize inputs, the extent of rabies-induced transcriptional changes in distinct neuronal cell types remains unclear and whether these changes preclude characterization of rabies-infected neurons according to established transcriptomic cell types is unknown. We used single-nucleus RNA sequencing to survey the gene expression profiles of rabies-infected neurons and assessed their correspondence with established transcriptomic cell types. We demonstrated that when using transcriptome-wide RNA profiles, rabies-infected cortical neurons can be transcriptomically characterized despite global and cell-type-specific rabies-induced transcriptional changes. Notably, we found differential modulation of neuronal marker gene expression, suggesting that caution should be taken when attempting to characterize rabies-infected cells with single genes or small gene sets.
2022-05-25 | GSE196771 | GEO