Project description:Enterovirus 71 (EV71) is one of the major pathogens associated with human hand, foot, and mouth disease (HFMD) and in some countries this pathogen is the leading cause of this disease. We previously found that CA16 could induce neurological disorders in young gerbils, which could serve as a good animal model for studying the neuropathogenesis of CA16 infection. In this study, we found that 1039 genes were up-regulated and 299 genes were down-regulated in CA16-infected gerbils compared with control. Differentially expressed genes were clustered into functional pathways and the top five pathways according to the enrich factor were viral myocarditis, type 1 diabetes mellitus, toxoplasmosis, toll-like receptor signaling pathway and TNF signaling pathway. Our results provide novel insight into the neuropathogenesis of HFMD induced by CA16 infection.
Project description:Coxsackievirus A16 (CA16) is one of the major pathogens associated with human hand, foot, and mouth disease (HFMD) and in some countries this pathogen is the leading cause of this disease. We previously found that CA16 could induce neurological disorders in young gerbils, which could serve as a good animal model for studying the neuropathogenesis of CA16 infection. In this study, we found that 1039 genes were up-regulated and 299 genes were down-regulated in CA16-infected gerbils compared with control. Differentially expressed genes were clustered into functional pathways and the top five pathways according to the enrich factor were viral myocarditis, type 1 diabetes mellitus, toxoplasmosis, toll-like receptor signaling pathway and TNF signaling pathway. Our results provide novel insight into the neuropathogenesis of HFMD induced by CA16 infection.
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:To investigate the transcriptional response of brainstem endothelial cells to mild respiratory infection, 12-month-old male C57Bl/6 mice were intranasally inoculated with SARS-CoV-2 MA10 strain or with saline.
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: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: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:We performed comprehensive miRNA profiling in EV71- and CA16-infected human umbilical vein endothelial cells (HUVECs) at multiple time points using high-throughput sequencing. The results showed that 135 known miRNAs exhibited remarkable differences in expression. Of these, 30differentially expressed miRNAs presented opposite trends in EV71- and CA16-infected samples. Subsequently, we mainly focused on the 30 key differentially expressed miRNAs through further screening to predict targets.Gene ontology (GO) and pathway analysis of the predicted targets showed the enrichment of 14 biological processes, 9 molecular functions, 8 cellular components, and 85 pathways. The regulatory networks of these miRNAs with predicted targets, GOs, pathways, and coexpression genes were determined, suggesting that miRNAs display intricate regulatory mechanisms during the infection phase. Consequently, we specifically analyzed the hierarchical GO categories of the predicted targets involved in biological adhesion. The results indicated that the distinct changes induced by EV71 and CA16 infection may be partly linked to the function of the blood-brain barrier. Taken together, this is the first report describing miRNA expression profiles in HUVECs with EV71 and CA16 infections using high-throughput sequencing. Our data provide useful insights that may help to elucidate the different host-pathogen interactions following EV71 and CA16 infection and offer novel therapeutic targets for these infections.
Project description:Enterovirus 71 (EV71) infection causes a profound shutoff of cellular protein synthesis. Deep RNA-sequencing and ribosome profiling were employed to systematically analyze messenger RNA and ribosome-protected RNA in EV71-infected rhabdomyosarcoma cells at progressive time points following infection. The analysis characterized the dynamic transcriptional and translational landscapes of both the virus and host cells. The results indicated that reduced translation of cellular mRNAs played a key role in EV71-induced host shutoff rather than mRNA depletion. During the host shutoff, EV71 protein was preferably synthesized through both a translational advantage and abundant mRNA production. Moreover, a small number of cellular genes were resistant to the host shutoff through both transcriptional and translational regulation, including genes in mitogen-activated protein kinase (MAPK) signaling pathway that is important for EV71 replication. These results indicated selective cellular protein synthesis during EV71-induced host shutoff as a mechanism the virus utilizes to benefit its replication.