Coxsackievirus B4 Transplacental Infection Severely Disturbs Central Tolerogenic Mechanisms in the Fetal Thymus.

Thymus plays a fundamental role in central tolerance establishment, especially during fetal life, through the generation of self-tolerant T cells. This process consists in T cells education by presenting them tissue-restricted autoantigens promiscuously expressed by thymic epithelial cells (TECs), thus preventing autoimmunity. Thymus infection by Coxsackievirus B (CV-B) during fetal life is supposed to disturb thymic functions and, hence, to be an inducing or accelerating factor in the genesis of autoimmunity.

Cytotoxicity and Antiviral Activities of Haplophyllum tuberculatum Essential Oils, Pure Compounds, and Their Combinations against Coxsackievirus B3 and B4.

is a plant commonly used in folk medicine to treat several diseases including vomiting, nausea, infections, rheumatism, and gastric pains. In the current study, essential oils, hydrosols, the pure compounds -(+)-limonene, -(-)-limonene, and 1-octanol, as well as their combinations -(+)-limonene/1-octanol and -(-)-limonene/1-octanol, were screened for their cytotoxicity on HEp-2 cells after 24, 48, and 72 h, and then tested for their activity against Coxsackievirus B3 and B4 (CV-B3 and CV-B4) at 3 different moments: addition of the plant compounds before, after, or together with virus inoculation. Results showed that the samples were more cytotoxic after 72 h than after 24 h or 48 h cell contact.

Effect of Coxsackievirus B4 Infection on the Thymus: Elucidating Its Role in the Pathogenesis of Type 1 Diabetes.

The thymus gland is a primary lymphoid organ for T-cell development. Various viral infections can result in disturbance of thymic functions. Medullary thymic epithelial cells (mTECs) are important for the negative selection of self-reactive T-cells to ensure central tolerance.

Modulation of IGF2 Expression in the Murine Thymus and Thymic Epithelial Cells Following Coxsackievirus-B4 Infection.

Coxsackievirus B4 (CV-B4) can infect human and murine thymic epithelial cells (TECs). In a murine TEC cell line, CV-B4 can downregulate the transcription of the insulin-like growth factor 2 () gene coding for the self-peptide of the insulin family. In this study, we show that CV-B4 infections of a murine TEC cell line decreased P3 promoter activity by targeting a region near the transcription start site; however, the stability of transcripts remained unchanged, indicating a regulation of transcription.

Type B coxsackieviruses and central nervous system disorders: critical review of reported associations.

Type B coxsackieviruses (CV-B) frequently infect the central nervous system (CNS) causing neurological diseases notably meningitis and encephalitis. These infections occur principally among newborns and children. Epidemiological studies of patients with nervous system disorders demonstrate the presence of infectious virus, its components, or anti-CV-B antibodies.

Coxsackievirus B4 infection and interneuronal spread in primary cultured neurons.

Coxsackie B viruses (CV-B) are usually transmitted via the fecal-oral route and the virus gains the central nervous system (CNS) via the bloodstream. Nevertheless, other routes of spread of the virus to the CNS cannot be excluded, including the neuronal route. Neuronal cells, as well as non-neuronal cells (fibroblasts), were isolated from mice and inoculated with CV-B4 in the absence and presence of neutralizing serum.

Assessment of Thymic Output Dynamics After Infection of Mice With Coxsackievirus B4.

The thymus is the main organ of the lymphatic system, in which T cells undergo a rigorous selection to ensure that their receptors (TCRs) will be functional and will not react against the self. Genes encoding for TCR chains are fragmented and must be rearranged by a process of somatic recombination generating TCR rearrangement excision circles (TRECs). We recently documented coxsackievirus B4 (CV-B4) infection of Swiss albino mouse thymus in the course of transmission.

Housekeeping Gene Expression in the Fetal and Neonatal Murine Thymus Following Coxsackievirus B4 Infection.

The thymus fulfills the role of T-cell production and differentiation. Studying transcription factors and genes involved in T-cell differentiation and maturation during the fetal and neonatal periods is very important. Nevertheless, no studies to date have been interested in evaluating the expressions of housekeeping genes as internal controls to assess the varying expressions of different genes inside this tissue during that period or in the context of viral infection.

Immunopathology in the brain of mice following vertical transmission of Coxsackievirus B4.

Coxsackie B viruses (CV-B) are associated with several central nervous system (CNS) disorders. These viruses are predominantly transmitted by fecal-oral route but vertical transmission can also occur. This work attempted to study the immune response ensuing vertical transmission of CV-B to the brain, and its eventual implementation in the brain pathogenesis.

Impact of coxsackievirus-B4E2 combined with a single low dose of streptozotocin on pancreas of outbred mice: investigation of viral load, pathology and inflammation.

Coxsackieviruses B (CV-B) belong to the EV-B species. CV-B and particularly CV-B4 are thought to be involved in the development of chronic diseases like type 1 diabetes (T1D). The mechanisms of the enteroviral pathogenesis of T1D are not well known, yet.

The presentation of neuroendocrine self-peptides in the thymus: an essential event for individual life and vertebrate survival.

Confirming Burnet's early hypothesis, elimination of self-reactive T cells in the thymus was demonstrated in the late 1980s, and an important question immediately arose about the nature of the self-peptides expressed in the thymus. Many genes encoding neuroendocrine-related and tissue-restricted antigens (TRAs) are transcribed in thymic epithelial cells (TECs). They are then processed for presentation by proteins of the major histocompatibility complex (MHC) expressed by TECs and thymic dendritic cells.

Coxsackievirus-B4E2 can infect monocytes and macrophages in vitro and in vivo.

Viral RNA (vRNA) is found in mice inoculated with coxsackievirus-B4E2 (CV-B4E2). The CV-B4E2 infection of murine spleen cells in vitro is enhanced with CV-B4E2-infected mouse serum. It has been investigated whether monocyte/macrophages were targets of CV-B4E2 in mice.

Evaluation of Contamination Risks with Coxsackievirus B4 E2 in Swiss Albino Mice Stools.

Coxsackie B4 (CV-B4), is a major cause of viral myocarditis, dilated cardiomyopathy, and pancreatitis. Like other human enteroviruses, CV-B4 is ubiquitous, excreted in the stool, transmitted by fecal-oral route, and persists in the environment. In the context of studies on CV-B4 infection, it is important to investigate how this virus can be eliminated and to show the possibility of contamination risk with a CV-B4 E2 infected Swiss albino mice.

Coxsackievirus B4 vertical transmission in a murine model.

Background: Life-threatening infections with type B Coxsackieviruses (CV-B) are frequently encountered among newborns and are partly attributed to vertically-transmitted virus. Our current study investigates this alternative way of contamination by CV-B, using a mouse model.

Methods: Pregnant Swiss mice were intraperitoneally inoculated with CV-B4 E2 at gestational day 10(G) or 17G.

Anti-coxsackievirus B4 (CV-B4) enhancing activity of serum associated with increased viral load and pathology in mice reinfected with CV-B4.

In previous studies it was shown that inoculation of Swiss albino mice with CV-B4 E2 resulted in the production of serum IgG capable of enhancing the CV-B4 E2 infection of murine spleen cells cultures. To investigate whether such an enhancing activity of serum can play a role in vivo, we decided to study the CV-B4 E2 infection in mice exposed to successive inoculations of virus. In Swiss albino mice infected with CV-B4 E2 at the age of 21 days, anti-CV-B4 E2 neutralizing and enhancing activities of their serum peaked after 55 d.

In-utero coxsackievirus B4 infection of the mouse thymus.

Type B coxsackievirus (CV-B) infections are involved frequently in the triggering of several autoimmune diseases such as myocarditis, dilated cardiomyopathy, pericarditis, pancreatitis, type 1 diabetes, encephalitis, thyroiditis or Sjögren's syndrome. Serological and virological evidence suggests that maternal infections during pregnancy can play a role in the appearance of these diseases in offspring. The current study aims to explore the effect of an in-utero CV-B infection on the fetal thymus, the central site for programming immunological self-tolerance.

Central nervous system infection following vertical transmission of Coxsackievirus B4 in mice.

Coxsackie B viruses (CV-B) are important pathogens associated with several central nervous system (CNS) disorders. CV-B are mainly transmitted by the faecal-oral route, but there is also evidence for vertical transmission. The outcome of in utero CV-B infections on offspring's CNS is poorly explored.

Immunoglobulin G-dependent enhancement of the infection with Coxsackievirus B4 in a murine system.

It was demonstrated that specific IgG can enhance the infection with CV-B4, in vitro, in the human system. This enhancement could be involved in the pathophysiology of CV-B4 induced diseases. To investigate further the role of enhancing IgG in the infection with CV-B4 E2 in vivo, animal models are needed.

How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?

Through synthesis and presentation of neuroendocrine self-antigens by major histocompatibility complex proteins, thymic epithelial cells (TECs) play a crucial role in programing central immune self-tolerance to neuroendocrine functions. Insulin-like growth factor-2 (IGF-2) is the dominant gene/polypeptide of the insulin family that is expressed in TECs from different animal species and humans. Igf2 transcription is defective in the thymus of diabetes-prone bio-breeding rats, and tolerance to insulin is severely decreased in Igf2 (-/-) mice.

Enteroviral central nervous system infections in children of the region of monastir, Tunisia: diagnosis, laboratory findings of cerebrospinal fluid and clinical manifestations.

Human enteroviruses (HEV) are one of the major causes of central nervous system (CNS) infections in pediatrics. A prospective study was conducted to assess the epidemiological, clinical, and laboratory characteristics of enterovirus (EV) infections of the CNS in children under 15-years-old, suspected of having viral CNS infections and admitted to the Pediatric Department of Monastir University Hospital, Tunisia. Enteroviral RNA was detected by 5' NCR nested RT-PCR assay in 33 % (20 out of 60) of cerebrospinal fluid specimens, whereas only six samples (10 %) were EV positive in cell culture.

Persistent infection of thymic epithelial cells with coxsackievirus B4 results in decreased expression of type 2 insulin-like growth factor.

It has been hypothesized that a disturbance of central self-tolerance to islet β cells may play a role in the enteroviral pathogenesis of type 1 diabetes. Whether enteroviruses can induce an impaired expression of β-cell self-antigens in thymic epithelial cells has been investigated in a murine thymic epithelial (MTE) cell line. This cell line was permissive to the diabetogenic group B4 coxsackievirus (CV-B4) strain CV-B4 E2 and spontaneously expressed type 2 insulin-like growth factor (Igf2), the dominant self-antigen of the insulin family.

Prolonged viral RNA detection in the central nervous system of one-week-old Swiss albino mice following coxsackievirus B4 and echovirus 9 infection.

Objectives: Type B coxsackieviruses (CV-B), together with echoviruses (E), are among the most common pathogens encountered in aseptic meningitis and meningoencephalitis. They frequently infect the central nervous system (CNS). The mechanisms of virus spreading in the CNS are poorly understood.

Immunology in the clinic review series; focus on type 1 diabetes and viruses: role of antibodies enhancing the infection with Coxsackievirus-B in the pathogenesis of type 1 diabetes.

Type 1 diabetes results from an interaction between genetic and environmental factors. Coxsackieviruses B (CV-B) are major environmental candidates, as suggested by epidemiological and experimental studies. The mechanisms leading to the disease involve interactions between the virus, host target tissue (pancreas) and the immune system.

Immunology in the clinic review series; focus on type 1 diabetes and viruses: enterovirus, thymus and type 1 diabetes pathogenesis.

Thymus dysfunction, especially immune suppression, is frequently associated with various virus infections. Whether viruses may disturb the thymus function and play a role in the pathogenesis of autoimmune diseases is an open issue. Enteroviruses, especially Coxsackievirus B4 (CV-B4), have been largely suggested as potential inducers or aggravating factors of type 1 diabetes (T1D) pathogenesis in genetically predisposed individuals.

Enteroviruses and type 1 diabetes: towards a better understanding of the relationship.

Environmental factors, especially viruses, are involved in the initiation or the acceleration of type 1 diabetes (T1D) pathogenesis. Epidemiological data strongly suggest that enteroviruses, such as coxsackievirus B4 (CV-B4), can be associated with T1D. It has been demonstrated that enterovirus infections were significantly more prevalent in at risk individuals, such as siblings of diabetic patients, when they developed anti-beta-cell autoantibodies or T1D, and in recently diagnosed diabetic patients, compared with control subjects.