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Article: Vers une meilleure compréhension de la relation entre entérovirus et diabète de type 1.

Jaïdane, H / Goffard, A / Gharbi, J / Hober, D

2022 Volume 12, Issue 3, Page(s) 187–200

Abstract: Environmental factors, especially viruses, are involved in the initiation or the acceleration of type 1 diabetes (T1D) pathogenesis. Epidemiological data strongly suggest that enteroviruses, like coxsackievirus B4 (CV-B4), can be associated with T1D. It ... ...

Title translation	Relationship between enteroviruses and diabetes.
Abstract	Environmental factors, especially viruses, are involved in the initiation or the acceleration of type 1 diabetes (T1D) pathogenesis. Epidemiological data strongly suggest that enteroviruses, like 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-b cells autoantibodies or T1D, and in recently diagnosed diabetic patients, compared with control subjects. The isolation of CV-B4 from the pancreas of diabetic patients strengthened the hypothesis of a relationship between the virus and the disease. Studies performed in vitro and in vivo in animal models helped in discovering mechanisms of the infection of pancreas and other tissues, able to play a role in the pathogenesis of T1D. Interestingly, it cannot be excluded that enteroviruses behave as half-devil half-angel since experimental studies suggest that, in certain conditions, these agents would be able to protect individuals against the disease.
Language	French
Publishing date	2022-09-21
Publishing country	France
Document type	English Abstract ; Journal Article
ZDB-ID	2118387-9
ISSN	1950-6961 ; 1267-8694
ISSN (online)	1950-6961
ISSN	1267-8694
DOI	10.1684/12-3.2011.11043
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Article ; Online: Type B coxsackieviruses and central nervous system disorders: critical review of reported associations.

Jmii, Habib / Fisson, Sylvain / Aouni, Mahjoub / Jaidane, Hela

Reviews in medical virology

2020 Volume 31, Issue 4, Page(s) e2191

Abstract: 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 ... ...

Abstract	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. Some experimental studies conducted in vitro and in vivo support the potential association between CV-B and idiopathic neurodegenerative diseases such as amyotrophic lateral sclerosis and psychiatric illness such as schizophrenia. However, mechanisms explaining how CV-B infections may contribute to the genesis of CNS disorders remain unclear. The proposed mechanisms focus on the immune response following the viral infection as a contributor to pathogenesis. This review describes these epidemiological and experimental studies, the modes of transmission of CV-B with an emphasis on congenital transmission, the routes used by CV-B to reach the brain parenchyma, and plausible mechanisms by which CV-B may induce CNS diseases, with a focus on potential immunopathogenesis.
MeSH term(s)	Antibodies, Viral ; Brain/virology ; Central Nervous System Diseases/epidemiology ; Central Nervous System Diseases/etiology ; Central Nervous System Diseases/virology ; Central Nervous System Infections/virology ; Child ; Coxsackievirus Infections/diagnosis ; Coxsackievirus Infections/pathology ; Enterovirus B, Human/immunology ; Enterovirus B, Human/isolation & purification ; Humans ; Infant, Newborn
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2020-11-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1086043-5
ISSN	1099-1654 ; 1052-9276
ISSN (online)	1099-1654
ISSN	1052-9276
DOI	10.1002/rmv.2191
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Zs.A 3308: Show issues

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Article: Role of coxsackievirus B4 in the pathogenesis of type 1 diabetes.

Jaïdane, H / Hober, D

Diabetes & metabolism

2008 Volume 34, Issue 6 Pt 1, Page(s) 537–548

Abstract: Environmental factors, especially viruses, are thought to play an important role in the initiation or acceleration of the pathogenesis of type 1 diabetes (T1D). Data from retrospective and prospective epidemiological studies strongly suggest that ... ...

Abstract	Environmental factors, especially viruses, are thought to play an important role in the initiation or acceleration of the pathogenesis of type 1 diabetes (T1D). Data from retrospective and prospective epidemiological studies strongly suggest that enteroviruses, such as coxsackievirus B4 (CV-B4), may be associated with the development of T1D. It has also been shown that enterovirus infections are significantly more prevalent in at-risk individuals such as the siblings of diabetic patients, when they develop anti-beta-cell autoantibodies or T1D, and in recently diagnosed diabetic patients, compared with control subjects. The isolation of CV-B4 from the pancreas of diabetic patients supports the hypothesis of a relationship between the virus and the disease. Furthermore, studies performed in vitro and in vivo in animal models have increased our knowledge of the role of CV-B4 in T1D by helping to clarify the pathogenic mechanisms of the infection that can lead to beta-cell destruction, including direct virus-induced beta-cell lysis, molecular mimicry, 'bystander activation' and viral persistence. The role of enteroviruses as the sole agents in T1D, and a causal link between these agents and T1D, have not yet been established, although arguments that support such a role for these viruses in the pathogenesis of the disease cannot be ignored.
MeSH term(s)	Animals ; Bystander Effect ; Coxsackievirus Infections/complications ; Diabetes Mellitus, Type 1/epidemiology ; Diabetes Mellitus, Type 1/virology ; Disease Models, Animal ; Enterovirus B, Human/pathogenicity ; Enterovirus B, Human/physiology ; Humans ; Insulin-Secreting Cells/pathology ; Insulin-Secreting Cells/virology ; Prospective Studies ; Retrospective Studies ; Virus Replication
Language	English
Publishing date	2008-12
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1315751-6
ISSN	1262-3636 ; 0338-1684
ISSN	1262-3636 ; 0338-1684
DOI	10.1016/j.diabet.2008.05.008
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Zs.A 1267: Show issues

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Article ; Online: Immunopathology in the brain of mice following vertical transmission of Coxsackievirus B4.

Jmii, Habib / Halouani, Aymen / Abdeli, Mariem / Aouni, Mahjoub / Fisson, Sylvain / Jaïdane, Hela

Microbial pathogenesis

2020 Volume 140, Page(s) 103965

Abstract: 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 ... ...

Abstract	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. To this end, pregnant Swiss albino mice were inoculated with CV-B4 E2 or with sterile medium for control animals. At different ages after birth, brains were collected and analyzed for virus infection, histopathological changes and immune response. Infectious particles were detected in offspring's brain which demonstrates vertical transmission of the virus. This infection is persistent since the long lasting detection of viral RNA in offspring's brain. Some pathological signs including meningitis, edema and accumulation of inflammatory cells within and surrounding the inflammatory areas were observed. Immunoflorescence staining unveiled the presence of T lymphocytes and microgliosis in the sites of lesion for a long period after birth. Multiplex cytokines measurement upon supernatants of in vitro mixed brain cells and extracted mononuclear cells from offspring's brain has demonstrated an elevated secretion of the pro-inflammatory cytokines TNFα, IL-6 and IFNα and the chemokines RANTES and MCP-1. Hence, vertical transmission of CV-B4 and its persistence within offspring's brain can lead to pathological features linked to increased and sustained immune response.
MeSH term(s)	Animals ; Brain/immunology ; Brain/pathology ; Brain/virology ; Coxsackievirus Infections/immunology ; Coxsackievirus Infections/pathology ; Coxsackievirus Infections/transmission ; Coxsackievirus Infections/virology ; Cytokines/genetics ; Cytokines/immunology ; Enterovirus B, Human/genetics ; Enterovirus B, Human/physiology ; Female ; Humans ; Infectious Disease Transmission, Vertical ; Interferon-alpha/genetics ; Interferon-alpha/immunology ; Male ; Mice ; Pregnancy ; Pregnancy Complications, Infectious/genetics ; Pregnancy Complications, Infectious/immunology ; Pregnancy Complications, Infectious/pathology ; Pregnancy Complications, Infectious/virology ; T-Lymphocytes/immunology
Chemical Substances	Cytokines ; Interferon-alpha
Language	English
Publishing date	2020-01-03
Publishing country	England
Document type	Journal Article
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2020.103965
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Zs.A 2136: Show issues

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Article ; Online: Coxsackievirus-B4E2 can infect monocytes and macrophages in vitro and in vivo.

Benkahla, M A / Elmastour, F / Sane, F / Vreulx, A-C / Engelmann, I / Desailloud, R / Jaidane, H / Alidjinou, E K / Hober, D

Virology

2018 Volume 522, Page(s) 271–280

Abstract: 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- ...

Abstract	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. vRNA has been detected in spleen and bone marrow of infected animals. The levels of vRNA were higher in CD14+ cells than in CD14- spleen cells and in F4/80- cells than in F4/80+ spleen cells. Meanwhile, CD14+ cells and F4/80- cells were more permissive to CV-B4E2 in vitro and the infection was enhanced when the virus was mixed with immune serum. While CV-B4E2 infected BMDM cultures (98% F4/80+); however, the immune serum did not enhance the infection. In conclusion, CV-B4E2 infects monocytes (CD14+, F4/80-) and macrophages (CD14+, F4/80+) in vivo and immune serum can enhance the in vitro infection of these cells arising out of the spleen.
MeSH term(s)	Animals ; Antibody-Dependent Enhancement ; Bone Marrow/virology ; Coxsackievirus Infections/virology ; Disease Models, Animal ; Enterovirus B, Human/growth & development ; Macrophages/virology ; Mice ; Monocytes/virology ; RNA, Viral/analysis ; Spleen/virology
Chemical Substances	RNA, Viral
Language	English
Publishing date	2018-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2018.06.010
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Ud II Zs.172: Show issues

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

Michaux, Hélène / Halouani, Aymen / Trussart, Charlotte / Renard, Chantal / Jaïdane, Hela / Martens, Henri / Geenen, Vincent / Hober, Didier

Microorganisms

2021 Volume 9, Issue 2

Abstract: 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 ( ...

Abstract	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 (
Language	English
Publishing date	2021-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9020402
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Article ; Online: Cytotoxicity and Antiviral Activities of Haplophyllum tuberculatum Essential Oils, Pure Compounds, and Their Combinations against Coxsackievirus B3 and B4.

Hamdi, Assia / Halouani, Aymen / Aouf, Ines / Viaene, Johan / Marzouk, Belsem / Kraiem, Jamil / Jaïdane, Hela / Heyden, Yvan Vander

Planta medica

2021 Volume 87, Issue 10-11, Page(s) 827–835

Abstract: Haplophyllum ... ...

Abstract	Haplophyllum tuberculatum
MeSH term(s)	Antiviral Agents/pharmacology ; Limonene ; Oils, Volatile/pharmacology ; Plant Extracts/pharmacology ; Rutaceae
Chemical Substances	Antiviral Agents ; Oils, Volatile ; Plant Extracts ; Limonene (9MC3I34447)
Language	English
Publishing date	2021-07-22
Publishing country	Germany
Document type	Journal Article
ZDB-ID	123545-x
ISSN	1439-0221 ; 0032-0943
ISSN (online)	1439-0221
ISSN	0032-0943
DOI	10.1055/a-1538-5289
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Uf I Zs.157: Show issues

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Article ; Online: Housekeeping Gene Expression in the Fetal and Neonatal Murine Thymus Following Coxsackievirus B4 Infection.

Halouani, Aymen / Jmii, Habib / Michaux, Hélène / Renard, Chantal / Martens, Henri / Pirottin, Dimitri / Mastouri, Maha / Aouni, Mahjoub / Geenen, Vincent / Jaïdane, Hela

Genes

2020 Volume 11, Issue 3

Abstract: 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 ... ...

Abstract	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. Thus, we evaluated by real-time quantitative polymerase chain reaction (qPCR) the expression of the most common internal control genes in the thymus of Swiss albino mice during the fetal and neonatal period, and following in utero infection with Coxsackievirus B4. The stability of expression of these reference genes in different samples was investigated using the geNorm application. Results demonstrated that the expression stability varied greatly between genes.
MeSH term(s)	Animals ; Coxsackievirus Infections/genetics ; Coxsackievirus Infections/metabolism ; Genes, Essential ; Mice ; Proteins/genetics ; Proteins/metabolism ; Thymus Gland/metabolism ; Transcriptome
Chemical Substances	Proteins ; ornithine decarboxylase antizyme
Language	English
Publishing date	2020-03-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes11030279
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Article ; Online: Assessment of Thymic Output Dynamics After

Halouani, Aymen / Jmii, Habib / Bodart, Gwennaëlle / Michaux, Hélène / Renard, Chantal / Martens, Henri / Aouni, Mahjoub / Hober, Didier / Geenen, Vincent / Jaïdane, Hela

Frontiers in immunology

2020 Volume 11, Page(s) 481

Abstract: 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 ... ...

Abstract	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
MeSH term(s)	Animals ; Autoimmune Diseases/immunology ; Autoimmunity ; Cell Differentiation ; Cell Proliferation ; Coxsackievirus Infections/immunology ; Coxsackievirus Infections/transmission ; Down-Regulation ; Enterovirus/pathogenicity ; Enterovirus/physiology ; Female ; Genes, T-Cell Receptor beta/genetics ; Infectious Disease Transmission, Vertical ; Male ; Mice ; Receptor Protein-Tyrosine Kinases/genetics ; Receptor Protein-Tyrosine Kinases/metabolism ; Thymus Gland/physiology ; Thymus Gland/virology ; Uterus/immunology ; Uterus/virology ; Viral Load
Chemical Substances	Ptk7 protein, mouse (EC 2.7.10.1) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2020-04-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.00481
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Article ; Online: Coxsackievirus B4 infection and interneuronal spread in primary cultured neurons.

Jmii, Habib / Halouani, Aymen / Maatouk, Mouna / Chekir-Ghedira, Leila / Aouni, Mahjoub / Fisson, Sylvain / Jaïdane, Hela

Microbial pathogenesis

2020 Volume 145, Page(s) 104235

Abstract: 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 ... ...

Abstract	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. In the absence of neutralizing serum, virus titers recorded in neuron cultures and rates of infected neurons were non-significantly different compared to those recorded in fibroblast cultures. Higher cell mortality was noted among neurons than fibroblasts. The addition of neutralizing serum to neurons did not reduce significantly virus titers or rates of infected cells and cell viability was not significantly augmented, while virus titers and rates of infected fibroblasts were significantly reduced and their viability was significantly enhanced as well. Our results demonstrate the ineffectiveness of neutralizing serum to prevent neurons infection with CV-B4 which suggests a trans-synaptic transmission of CV-B4 between neurons.
MeSH term(s)	Animals ; Central Nervous System ; Coxsackievirus Infections ; Enterovirus B, Human ; Mice ; Neurons ; Viral Load
Language	English
Publishing date	2020-04-28
Publishing country	England
Document type	Journal Article
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2020.104235
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