Project description:Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are the predominant etiological agents of hand, foot, and mouth disease (HFMD) and both belong to the human enterovirus A species of the Picornaviridae family. These viruses share similar genetic homology, although the clinical manifestations of HFMD caused by the two viruses have some discrepancies. Furthermore, the underlying mechanisms leading to these differences remain unclear. microRNAs (miRNAs) participate in numerous biological or pathological processes, including host responses to viral infections, by targeting messenger RNAs (mRNAs) for translational repression or degradation. Here, we focused on differences in miRNA expression patterns in peripheral blood mononuclear cells (PBMCs) of rhesus monkeys infected with EV71 or CA16 at different time points using high-throughput sequencing technology. For the first time, this study demonstrated that EV71 and CA16 infection result in specific miRNA expression patterns in PBMCs.
Project description:Enterovirus 71 (EV71), a member of the Enterovirus genus in the Picornaviridae family, was first recognized as a dermotrophic virus that usually cause mild, self-limiting hand-foot-and-mouth disease (HFMD). However, EV71 infection can sometimes induce a variety of severe neurological complications, pulmonary edema and even death. Here, we aimed to provide an overview of proteomics characterization of EV71-infected brain and lung tissues.
Project description:Hand, foot and mouth disease (HFMD), caused by enterovirus 71 (EV71), presents mild to severe disease, and sometimes fatal neurological and respiratory manifestations. However, reasons for the severe pathogenesis remain undefined. To investigate this, infection and viral kinetics of EV71 isolates from clinical disease (mild, moderate and severe) from Sarawak, Malaysia, were characterized in human rhabdomyosarcoma (RD), neuroblastoma (SH-SY5Y) and peripheral blood mononuclear cells (PBMCs). High resolution transcriptomics was used to decipher EV71-host interactions in PBMCs. Ingenuity analyses revealed similar pathways triggered by all EV71 isolates, although the extent of activation varied. Importantly, several pathways were found to be specific to the severe isolate, including triggering receptor expressed on myeloid cells 1 (TREM-1) signaling. Depletion of TREM-1 in EV71-infected PBMCs with peptide LP17 resulted in decreased levels of pro-inflammatory genes, and reduced viral loads for the moderate and severe isolates. Mechanistically, this is the first report describing the transcriptome profiles during EV71 infections in primary human cells, and the involvement of TREM-1 in the severe disease pathogenesis, thus providing new insights for future treatment targets.
Project description:Enterovirus 71 (EV71) causes Hand, Foot, and Mouth Disease and has been clinically associated with neurological complications. However, there is a lack of relevant models to elucidate the neuropathology of EV71 and its mechanism, as the current models mainly utilize animal model or immortalized cell lines. In this study, we established a human motor neuron model for EV71 infection.
Project description:Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are major causative agents for hand, foot and mouth disease (HFMD). In China, more than 70,756 children were infected and 40 died from the disease in recent years. This study aimed to develop a protein chip that can simultaneously detect and differentiate the antibodies induced by EV71 and CA16 simultaneously. The structure protein vp1 and vp3 from the two viruses were purified and spotted onto an aldehyde groupmodified glass slide at 1mg/ml. After that, the protein chip was reacted with the corresponding positive serum against these viruses, hybridized with a Cy3-labeled secondary antibody and scanned using the popular GenePix 4000B Microarray Scanner. In this study, Both IgG and IgM serum antibody to EV71 and CA16 were detected using protein Chip. The results showed that this method could hybridize specifically with the corresponding antibodies with strong signals and without cross-hybridization. The data also confirmed the proposed method's specificity, sensitivity, and convenience. In conclusion, this protein chip can be used to differentiate the antibodies induced by the EV71and CA16.
Project description:Enterovirus 71 (EV71) is one of the leading causes of hand, foot and mouth disease with neurological complications in some cases. To study the pathogenesis of EV71 infection, large scale analyses of EV71 infected cells have been performed. However, most of these studies employed rhabdomyosarcoma (RD) cells or used transcriptomic strategy. Here, we performed SILAC-based quantitative proteomic analysis of EV71-infected U251 cells, a human glioma cell line. A total of 3,125 host proteins were quantified, 451 of which were differentially regulated as a result of EV71 infection at 8 hpi or 20 hpi or both.
2015-09-15 | PXD002454 | Pride
Project description:Genomic epidemiology of Coxsackievirus A24 in Coastal Kenya, 2024
Project description:Hand, foot, and mouth disease (HFMD) is caused by more than 20 pathogenic enteroviruses belonging to the Picornaviridae family and Enterovirus genus. Since the introduction of the EV71 vaccine in 2016, the number of HFMD cases caused by EV71 has decreased. However, cases of infections caused by other enteroviruses, such as coxsackievirus A6 (CA6) and CA10, have been increasing accordingly. In this study, we used a clinical isolate of CA6 to establish an intragastric infection mouse model using 7-day-old mice to mimic the natural transmission route, by which we investigated the differential gene expression profiles associated with virus infection and pathogenicity. After intragastric infection, mice exhibited hind limb paralysis symptoms and weight loss, similar to those reported for EV71 infection in mice. The skeletal muscle was identified as the main site of virus replication, with a peak viral load reaching 2.31 × 107 copies/mg at 5 dpi and increased infiltration of inflammatory cells. RNA sequencing analysis identified differentially expressed genes (DEGs) after CA6 infection. DEGs in the blood, muscle, brain, spleen, and thymus were predominantly enriched in immune system responses, including pathways such as Toll-like receptor signalling and PI3K-Akt signalling. Our study has unveiled the genes involved in the host immune response during CA6 infection, thereby enhancing our comprehension of the pathological mechanism of HFMD.
Project description:Detection of causal variant for thrombocytopenia and second hit causing malignant disease onset by next-generation sequencing. The sample was taken at MDS diagnosis, the illness later developed into AML.