CVB3

Intestinal tuft cells, a kind of epithelial immune cells, rapidly expand in response to pathogenic infections, which is associated with infection-induced interleukin 25 (IL-25) upregulation. However, the metabolic mechanism of IL-25-induced tuft cell expansion is largely unknown. Folate metabolism provides essential purine and methyl substrates for cell proliferation and differentiation. Thus, we aim to investigate the roles of folate metabolism playing in IL-25-induced tuft cell expansion by enteroviral infection and recombinant murine IL-25 (rmIL-25) protein-stimulated mouse models...

Coxsackievirus B3 (CVB3) is a non-enveloped, single-stranded, positive RNA virus known for its role in provoking inflammatory diseases that affect the heart, pancreas, and brain, leading to conditions such as myocarditis, pancreatitis, and meningitis. Currently, there are no FDA-approved drugs treating CVB3 infection; therefore, identifying potential molecular targets for antiviral drug development is imperative. In this study, we examined the possibility of activating the cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway, a cytosolic DNA-sensing pathway that triggers a type-I interferon (IFN) response, in inhibiting CVB3 infection...

Enterovirus A71 (EV-A71) is the main pathogen causing hand, foot and mouth disease (HFMD) in children and occasionally associated with neurological diseases such as aseptic meningitis, brainstem encephalitis (BE) and acute flaccid paralysis. We report here that cellular pseudokinase tribbles 3 (TRIB3) facilitates the infection of EV-A71 via dual mechanisms. In one hand, TRIB3 maintains the metabolic stability of scavenger receptor class B member 2 (SCARB2), the bona fide receptor of EV-A71, to enhance the infectious entry and spreading of the virus...

Calcium/calmodulin-dependent protein kinase II (CaMKII) has been demonstrated to be aberrantly activated in viral myocarditis (VMC), but the role of its subtype CaMKIIδ in VMC remains unclear.VMC mice and cardiomyocytes models were induced by Coxsackievirus B3 (CVB3) treatment. Mice that underwent sham surgery and saline-treated cardiomyocytes served as controls. Body weight, survival, left ventricular ejection fraction (LVEF), and fractional shortening (LVFS) were measured, and HE staining was performed to evaluate heart function in VMC mice model and sham control...

Background Myocarditis is an inflammation of the heart muscle most often caused by an immune response to viral infections. Sex differences in the immune response during myocarditis have been well described but upstream mechanisms in the heart that might influence sex differences in disease are not completely understood. Methods Male and female BALB/c wild type mice received an intraperitoneal injection of heart-passaged coxsackievirus B3 (CVB3) or vehicle control. Bulk-tissue RNA-sequencing was conducted to better understand sex differences in CVB3 myocarditis...

BACKGROUND: Dysregulated cell death machinery and an excessive inflammatory response in Coxsackievirus B3(CVB3)-infected myocarditis are hallmarks of an abnormal host response. Complement C4 and C3 are considered the central components of the classical activation pathway and often participate in the response process in the early stages of virus infection. METHODS: In our study, we constructed a mouse model of CVB3-related viral myocarditis via intraperitoneal injection of Fer-1 and detected myocarditis and ferroptosis markers in the mouse myocardium...

Viral myocarditis (VM) is a clinically common inflammatory disease. Accumulating literature has indicated that M2 macrophages protect mice from Coxsackievirus B3 (CVB3)-induced VM. However, mechanisms that underlie M2 macrophages alleviating myocardial inflammation remain largely undefined. We found that M2 macrophage-derived exosomes (M2-Exo) can effectively attenuate VM. The long non-coding RNA (lncRNA) AK083884 in M2-Exo was found to be involved in the regulation of macrophage polarization by exosome lncRNA sequencing combined with in vitro functional assays...

Viral myocarditis (VMC) is the major reason for sudden cardiac death among both children and young adults. Of these, coxsackievirus B3 (CVB3) is the most common causative agent of myocarditis. Recently, the role of signaling pathways in the pathogenesis of VMC has been evaluated in several studies, which has provided a new perspective on identifying potential therapeutic targets for this hitherto incurable disease. In the present study, in vivo and in vitro experiments showed that CVB3 infection leads to increased Bim expression and triggers apoptosis...

Due to seasonally appearing viruses and several outbreaks and present pandemic, we are surrounded by viruses in our everyday life. In order to reduce viral transmission, functionalized surfaces that inactivate viruses are in large demand. Here the endeavor was to functionalize cellulose-based materials with tannic acid (TA) and tannin-rich extracts by using different binding polymers to prevent viral infectivity of both non-enveloped coxsackievirus B3 (CVB3) and enveloped human coronavirus OC43 (HCoV-OC43)...

Acute viral myocarditis can progress to chronic myocarditis leading to dilated cardiomyopathy (DCM). Persistent CD4+ T-cell-mediated autoimmunity triggered by infection plays a critical role in this progression. Increasing evidence demonstrates that effector memory CD4+ T (CD4+ TEM ) cells, a subset of memory CD4+ T cells, are crucial pathogenic mediators of many autoimmune diseases. However, the role of CD4+ TEM cells during the progression from acute viral myocarditis to DCM remains unknown. In this study, we observed an increase in CD4+ TEM cells both in the periphery and the heart, and memory CD4+ T cells were the predominant sources of IL-17A and IFN-γ among inflamed heart-infiltrating CD4+ T cells during the progression from acute myocarditis to chronic myocarditis and DCM in CVB3-induced BALB/c mice...

Biological sex plays an integral role in the immune response to various pathogens. The underlying basis for these sex differences is still not well defined. Here, we show that Coxsackievirus B3 (CVB3) induces a viral-specific CD4 + T cell response that can protect female mice from mortality. We found that CVB3 can induce expansion of CD62L lo CD4 + T cells in the mesenteric lymph node and spleen of female but not male mice as early as 5 days post-inoculation, indicative of activation. Using a recombinant CVB3 virus expressing a model CD4 + T cell epitope, we found that this response is due to viral antigen and not bystander activation...

ETHNOPHARMACOLOGICAL RELEVANCE: Jingfang Granules (JFG) originate from the traditional herbal formula Jingfang Baidu powder. It has the effects of inducing sweating and dispelling wind. It is a classic medication used for treating external pathogenic factors and viral diseases. However, the therapeutic mechanism of JFG for viral myocarditis needs further clarification. AIM OF THE STUDY: This study aimed to explore the therapeutic efficacy of JFG on coxsackievirus B3-induced viral myocarditis (VMC), along with the elucidation of its underlying mechanisms...

Coxsackievirus B3 (CVB3), a single-stranded positive RNA virus, primarily infects cardiac myocytes and is a major causative pathogen for viral myocarditis (VMC), driving cardiac inflammation and organ dysfunction. However, whether and how myocardial damage is involved in CVB3-induced VMC remains unclear. Herein, we demonstrate that the CVB3 infection of cardiac myocytes results in the release of mitochondrial DNA (mtDNA), which functions as an important driver of cardiac macrophage inflammation through the stimulator of interferon genes (STING) dependent mechanism...

The oxidative stress induced by the accumulation of reactive oxygen species (ROS) can lead to cell aging and death. Equally, the skeletal muscle usually hosts enteroviral persistent infection in inflammatory muscle diseases. As excellent bioactive products, the exosomes derived from umbilical cord mesenchymal stem cells (ucMSCs) have been proven to be safe and have low immunogenicity with a potential cell-free therapeutic function. Here, exosomes derived from ucMSCs (ucMSC-EXO) were extracted and characterized...

Appendix has a distinct abundance of lymphatic cells and serves as a reservoir of microbiota which helps to replenish the large intestine with healthy flora. And it is the primary site of IgA induction, which shapes the composition of the intestinal microbiota. Recent population-based cohort studies report that appendectomy is associated with an increased risk of acute myocardial infarction and ischemic heart disease. Here, whether appendectomy has an effect on the occurrence and development of coxsackievirus B3 (CVB3)-induced viral myocarditis is studied...

Evidence is emerging on the roles of long noncoding RNAs (lncRNAs) as regulatory factors in a variety of viral infection processes, but the mechanisms underlying their functions in coxsackievirus group B type3 (CVB3)-induced acute viral myocarditis have not been explicitly delineated. We previously demonstrated that CVB3 infection decreases miRNA-21 expression; however, lncRNAs that regulate the miRNA-21-dependent CVB3 disease process have yet to be identified. To evaluate lncRNAs upstream of miRNA-21, differentially expressed lncRNAs in CVB3-infected mouse hearts were identified by microarray analysis and lncRNA/miRNA-21 interactions were predicted bioinformatically...

Viral myocarditis (VMC), commonly caused by coxsackievirus B3 (CVB3) infection, lacks specific treatments and leads to serious heart conditions. Current treatments, such as IFNα and ribavirin, show limited effectiveness. Herein, rather than inhibiting virus replication, this study introduces a novel cardiomyocyte sponge, intracellular gelated cardiomyocytes (GCs), to trap and neutralize CVB3 via a receptor-ligand interaction, such as CAR and CD55. By maintaining cellular morphology, GCs serve as sponges for CVB3, inhibiting infection...

Coxsackievirus B3 (CVB3), a serotype of enterovirus B, causes hand, foot, and mouth disease; pericarditis; and myocarditis. A benzene sulfonamide derivative is reported to have inhibitory activity against wild-type (WT) and eight mutants of the viral capsid of CVB3. Furthermore, the crystal structure of the complex formed between WT viral capsid of CVB3 and the derivative revealed binding at a novel druggable interprotomer pocket. We investigated how the compound could be a potent inhibitor of both WT and some mutants of CVB3 by determining binding to the viral capsid and the interaction energy with the binding pocket based on molecular dynamics simulations and density functional theory...

Objective: To explore the effect and mechanism of 1, 25(OH)2 D3 on myocardial inflammation induced by Coxsackie virus B3 (CVB3) in mice. Methods: Wild type (WT) and 1α-hydroxylase knockout [1(OH)ase-/- ] male mice were divided into four groups: WT group, WT+CVB3 group, 1(OH)ase-/- +CVB3 group and 1(OH)ase-/- +CVB3+VD3 group, with 8 mice in each group. The indicators for evaluating myocardial cell injury were examined by different methods. The mRNA levels of pro-inflammatory cytokines [interlenkin (IL)-1β, IL-6, interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α)] were determined by quantitative real-time PCR...

Sex is a significant contributor to the outcome of human infections. Males are frequently more susceptible to viral, bacterial, and fungal infections, often attributed to weaker immune responses. In contrast, a heightened immune response in females enables better pathogen elimination but leaves females more predisposed to autoimmune diseases. Unfortunately, the underlying basis for sex-specific immune responses remains poorly understood. Here, we show a sex difference in the CD8+ T cell response to an enteric virus, Coxsackievirus B3 (CVB3)...