Group B Coxsackie Disease in Children

Modlin, John F.; Rotbart, Harley A.

doi:10.1007/978-3-642-60687-8_4

Cited by 43 publications

(50 citation statements)

References 112 publications

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“…Although most of these infections are associated with a mild febrile illness or upper respiratory infection (Rotbart et al, 1999), enteroviruses can also cause severe, potentially fatal diseases such as acute flaccid paralysis [caused by CVB in 13 % of all cases (Saeed et al, 2007)], aseptic meningitis [caused by enteroviruses in up to 90 % of all cases (Rotbart, 1995)] or acute viral myocarditis with CVB3 as one of the primary causative agents (Baboonian et al, 1997;Kim et al, 2001;McManus et al, 1991). Whereas in adults acute CVB myocarditis is rarely lethal, children are particularly susceptible to diverse CVB infections with mortality rates due to myocarditis in the range of 30-50 % (Modlin & Rotbart, 1997). In most patients acute myocarditis is abrogated by the successful elimination of the virus, but in some patients the viruses may persist and thus, the disease may progress to chronic myocarditis and finally to dilated cardiomyopathy (DCM) (incidence of six per 100 000 in North America) (Codd et al, 1989;Klingel et al, 2004), with DCM accounting for approximately 50 % of all heart transplantations (Boucek et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Identification of HLA-A01- and HLA-A02-restricted CD8+ T-cell epitopes shared among group B enteroviruses

Weinzierl

Rudolf

Maurer

et al. 2008

Journal of General Virology

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Acute enteroviral infections ranging from meningitis, pancreatitis to myocarditis are common and normally well controlled by the host immune system comprising virus-specific CD8 + cytotoxic T lymphocytes (CTL). However, in some patients enteroviruses and especially coxsackieviruses of group B are capable of inducing severe chronic forms of diseases such as chronic myocarditis. Currently, it is not known whether divergences in the CTL-related immune response may contribute to the different outcome and course of enterovirus myocarditis. A pre-requisite for the study of CTL reactions in patients with acute and chronic myocarditis is the identification of CTL epitopes. In order to define dominant enterovirus CTL epitopes, we have screened, by using gamma interferon (IFN-c) ELISPOT, 62 HLA-A*01-and 59 HLA-A*02-positive healthy blood donors for pre-existing CTL reactions against 12 HLA-A*01 and 20 HLA-A*02 predicted CTL epitopes derived from coxsackieviruses of group B. Positive CTL reactions were verified by FACS analysis in a combined major histocompatibility complex-tetramer IFN-c staining. A total of 14.8 % of all donors reacted against one of the three identified epitopes MLDGHLIAFDY, YGDDVIASY or GIIYIIYKL. The HLA-A*02-restricted epitope ILMNDQEVGV was recognized by 25 % of all tested blood donors. For this peptide, we could demonstrate specific granzyme B secretion, a strong cytolytic potential and endogenous processing. All four epitopes were homologous in 36-92 % of group B enteroviruses, providing a strong basis for monitoring the divergence of T-cellbased immune responses in enterovirus-induced acute and chronic diseases.

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Section: Introductionmentioning

confidence: 99%

Identification of HLA-A01- and HLA-A02-restricted CD8+ T-cell epitopes shared among group B enteroviruses

Weinzierl

Rudolf

Maurer

et al. 2008

Journal of General Virology

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“…CVB also targets cells of the central nervous system and the pancreas, frequently leading to aseptic meningitis and pancreatitis (7,12,33,35,40). Overall, CVB infection can cause considerable morbidity and mortality, particularly in newborns and in young or immunocompromised individuals (35,52).The murine model of CVB3 infection is a valuable system for studying CVB pathogenesis and immunity, as mice infected with CVB develop diseases similar to those observed in humans (52, 53). Intraperitoneal inoculation of adult C57BL/6 mice with CVB3 results in systemic acute infection; viremia peaks on day 2 to 3 postinfection (p.i.…”

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confidence: 99%

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confidence: 99%

Enumeration and Functional Evaluation of Virus-Specific CD4 ⁺ and CD8 ⁺ T Cells in Lymphoid and Peripheral Sites of Coxsackievirus B3 Infection

Kemball

Harkins

Whitton

2008

J Virol

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Previous studies have suggested that coxsackievirus B (CVB) activates CD8؉ T cells in vivo, but the extent of this activation and the antigen specificity of the CD8 ؉ T cells remain uncertain. Furthermore, CVB-induced CD4 ؉ T-cell responses have not been carefully investigated. Herein, we evaluate CD8 ؉ and CD4 ؉ T-cell responses both in a secondary lymphoid organ (spleen) and in peripheral tissues (heart and pancreas), using a recombinant CVB3 (rCVB3.6) that encodes well-characterized CD8؉ and CD4 ؉ T-cell epitopes. Despite reaching high levels in vivo, rCVB3.6 failed to trigger a marked expansion of CD8 ؉ or CD4 ؉ T cells, and T-cell activation was surprisingly limited. Furthermore, epitope-specific effector functions could not be detected using highly sensitive in vivo and ex vivo assays. Moreover, major histocompatibility complex (MHC) class I tetramer analysis indicated that our inability to detect CVB3-specific CD8 ؉ T-cell responses could not be explained by the cells being dysfunctional. In contrast to naïve T cells, epitope-specific memory CD8؉ and CD4 ؉ T cells proliferated markedly, indicating that both of the rCVB3.6-encoded epitopes were presented by their respective MHC molecules in vivo. These data are consistent with the observation that several CVB3 proteins can limit the presentation of viral epitopes on the surface of infected cells and suggest that the level of MHC/peptide complex is sufficient to trigger memory but not naïve T cells. Finally, our findings have implications for the biological significance of cross-priming, a process thought by some to be important for the induction of antiviral CD8؉ T-cell responses.Coxsackieviruses are members of the picornavirus family and enterovirus genus, which includes type A and B coxsackieviruses, polioviruses, echoviruses, and other unclassified enteroviruses. Although the majority of type B coxsackievirus (CVB) infections in humans are subclinical or cause relatively mild disease (including rash, myalgia, or upper respiratory complications), CVB are important human pathogens, and a substantial proportion of infections can lead to severe-even lethal-acute and chronic diseases. In particular, CVB is the most common infectious cause of myocarditis, which can lead to dilated cardiomyopathy and cardiac failure (38,44,45). CVB also targets cells of the central nervous system and the pancreas, frequently leading to aseptic meningitis and pancreatitis (7,12,33,35,40). Overall, CVB infection can cause considerable morbidity and mortality, particularly in newborns and in young or immunocompromised individuals (35,52).The murine model of CVB3 infection is a valuable system for studying CVB pathogenesis and immunity, as mice infected with CVB develop diseases similar to those observed in humans (52, 53). Intraperitoneal inoculation of adult C57BL/6 mice with CVB3 results in systemic acute infection; viremia peaks on day 2 to 3 postinfection (p.i.), and infectious virus is cleared by 2 weeks p.i. (33,34). Control of CVB3 infection depends on both cell-mediated a...

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“…CVB 4 can cause a broad range of diseases, such as myocarditis, pancreatitis, hepatitis, aseptic meningitis, meningoencephalitis, gastroenteritis, necrotizing enterocolitis, pneumonia and even death in neonates [1]. Moreover, clinical symptoms such as myopericarditis and pleurodynia (Bornholm disease) are still distinct and are associated only with CVB 4 infections [2]. Until now, there are no enterovirus-specific vaccines or therapeutic agents available for clinical usage of CVB 4 infection [3].…”

Section: Introductionmentioning

confidence: 99%

In Vitro and in Vivo Studies of the Inhibitory Effects of Emodin Isolated from Polygonum cuspidatum on Coxsakievirus B4

et al. 2013

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Abstract:The lack of effective therapeutics for Coxsackievirus B 4 (CVB 4 ) infection underscores the importance of finding novel antiviral compounds. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is one of the natural anthraquinone derivatives obtained from the root and rhizome of Polygonum cuspidatum. In the present study, the possibility of using emodin as a potential antiviral to treat CVB 4 infection was explored in vitro and in mice. Emodin reduced CVB 4 entry and replication on Hep-2 cells in a concentration-and time-dependent manner, with a 50% effective concentration (EC 50 ) of 12.06 μM and selectivity index (SI) of 5.08, respectively. The inhibitory effect of emodin for CVB 4 entry and replication was further confirmed by a quantitative real time PCR (qPCR) assay. The results further showed that the mice orally treated with different dosages of emodin displayed a dose dependent increase of survival rate, body weight and prolonged mean time of death (MTD), accompanied by significantly decreased myocardial virus titers and pathologic scores/lesions. Moreover, emodin could inhibit CVB 4 -induced apoptosis in vitro and in vivo. Our results indicated that emodin could be used as potential antiviral in the post-exposure prophylaxis for CVB 4 infection.

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Group B Coxsackie Disease in Children

Cited by 43 publications

References 112 publications

Identification of HLA-A01- and HLA-A02-restricted CD8+ T-cell epitopes shared among group B enteroviruses

Identification of HLA-A01- and HLA-A02-restricted CD8+ T-cell epitopes shared among group B enteroviruses

Enumeration and Functional Evaluation of Virus-Specific CD4 ⁺ and CD8 ⁺ T Cells in Lymphoid and Peripheral Sites of Coxsackievirus B3 Infection

In Vitro and in Vivo Studies of the Inhibitory Effects of Emodin Isolated from Polygonum cuspidatum on Coxsakievirus B4

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Group B Coxsackie Disease in Children

Cited by 43 publications

References 112 publications

Identification of HLA-A*01- and HLA-A*02-restricted CD8+ T-cell epitopes shared among group B enteroviruses

Identification of HLA-A*01- and HLA-A*02-restricted CD8+ T-cell epitopes shared among group B enteroviruses

Enumeration and Functional Evaluation of Virus-Specific CD4 + and CD8 + T Cells in Lymphoid and Peripheral Sites of Coxsackievirus B3 Infection

In Vitro and in Vivo Studies of the Inhibitory Effects of Emodin Isolated from Polygonum cuspidatum on Coxsakievirus B4

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Identification of HLA-A01- and HLA-A02-restricted CD8+ T-cell epitopes shared among group B enteroviruses

Identification of HLA-A01- and HLA-A02-restricted CD8+ T-cell epitopes shared among group B enteroviruses

Enumeration and Functional Evaluation of Virus-Specific CD4 ⁺ and CD8 ⁺ T Cells in Lymphoid and Peripheral Sites of Coxsackievirus B3 Infection