Protective Role for Interferon-β in Coxsackievirus B3 Infection

Deonarain, Raj; Cerullo, Dante; Fuse, Koichi; Liu, Peter P.; Fish, Eleanor N.

doi:10.1161/01.cir.0000136824.73458.20

Cited by 151 publications

(117 citation statements)

References 20 publications

(18 reference statements)

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“…Immune surveillance mechanisms involving type I IFN responses [4,8,9], efficient antigen processing of CVB3 epitopes by cardiac immunoproteasomes [4] and potent CD8 1 T-cell responses [6] are crucial determinants in the disease progress in CVB3 myocarditis. Initiation of these antiviral immune responses strongly relies on the function of professional APCs.…”

Section: Short Communicationmentioning

confidence: 99%

Antigen‐presentation capacity of dendritic cells is impaired in ongoing enterovirus myocarditis

et al. 2011

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Coxsackievirus B3 (CVB3)‐infection is a frequent cause of acute myocarditis, which may result in chronic myocarditis and virus persistence. Investigation of the initial immune responses to CVB3 may shed light on the mechanisms that contribute to ongoing disease. DCs, as key professional APCs, were investigated in two MHC‐matched hosts: while C57BL/6 mice are resistant to chronic CVB3‐myocarditis, the A.BY/SnJ mouse strain exhibits susceptibility. DC maturation and activation were critically impaired in A.BY/SnJ mice, as reflected by the failure of DCs to induce co‐stimulatory molecules and cytokine/chemokine responses. MHC class I‐restricted antigen presentation via the cross‐presentation pathway was also affected in DCs from A.BY/SnJ mice. DC maturation involves the accumulation of DC aggresome‐like induced structures (DALISs) and the transient storage of defective ribosomal products (DRiPs). DCs from A.BY/SnJ mice showed permanent DALIS accumulation; the detection of poly‐ubiquitinylated CVB3 proteins in these DALISs suggested a limitation in the MHC class I antigenic supply in this host. In conclusion, ongoing chronic disease in A.BY/SnJ mice due to a failure to clear the virus may be attributed to defects in DC maturation/activation and DC MHC class I antigen processing.

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Section: Short Communicationmentioning

confidence: 99%

Antigen‐presentation capacity of dendritic cells is impaired in ongoing enterovirus myocarditis

et al. 2011

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“…The most interesting candidates in this region is the type I interferon gene cluster; already known to be Genetic control of viral myocarditis in mice M Aly et al involved in regulating myocarditis. 24,25,56 However, as all loci contain many potentially interesting candidate genes with known non-synonymous sequence polymorphisms, these regions require much refining before they can be dissected further.…”

Section: Genetic Control Of Viral Myocarditis In Micementioning

confidence: 99%

“…Secretion of interferon (IFN) type I seems to provide a strong antiviral response as shown by increased susceptibility in IFN-a/b receptor, and IFN-b knockout mice. 24,25 Here we have exploited mouse genomic resources together with mouse models exhibiting phenotypic difference in host susceptibility against CVB3 as a means to map genetic loci influencing disease. Such loci should encode genes and proteins important for the interactions between host and CVB3.…”

Section: Introductionmentioning

confidence: 99%

Complex genetic control of host susceptibility to coxsackievirus B3-induced myocarditis

et al. 2007

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The pathogenesis of viral myocarditis is a multifactorial process involving host genetics, viral genetics and the environment in which they interact. We have used a model of infection with coxsackievirus B3 (CVB3) to characterize the contribution of host genetics to viral myocarditis in mice of different genetic backgrounds but with a common H2 haplotype: A/J and B10.A-H2 a .Here we have used Evans blue dye as a quantitative biomarker for susceptibility to CVB3-induced myocarditis in addition to histopathological semiquantitative measures. We have found evidence of linkage between susceptibility to viral myocarditis and three loci. A locus on chromosome 1 centered on D1Mit200 was linked to sarcolemmal disruption in males (P ¼ 0.00005), a second locus on chromosome 4 centered on D4Mit81 was also linked to sarcolemmal disruption in males (P ¼ 0.0022). A third locus on distal chromosome 3 centered on D3Mit19 was linked to myocardial infiltration, with a logarithm of odds (LOD) score of 4.7 (P ¼ 0.0045), as well as sarcolemmal disruption in females (P ¼ 0.0015). These results provide strong evidence for the presence of loci contributing to the susceptibility of mice to viral myocarditis.

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“…Intense inflammatory response, including proinflammatory cytokine activation and immune cell infiltration, is often observed under those conditions and are thus suggested to be involved in cardiac damage such as left ventricular (LV) dysfunction and remodeling. Additionally, we and others have shown previously in experimental and clinical settings that the cytokine IFN-b can lead to an elimination of viral genomes and to an improvement of LV function in patients and animals with enteroviral or adenoviral persistence and LV dysfunction (6)(7)(8).…”

mentioning

confidence: 98%

TRIF Is a Critical Survival Factor in Viral Cardiomyopathy

Riad

Westermann

Zietsch

et al. 2011

The Journal of Immunology

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TRIF is a member of the innate immune system known to be involved in viral recognition and type I IFN activation. Because IFNs are thought to play an important role in viral myocarditis, we investigated the role of TRIF in induced myocarditis in mice. Whereas C57BL/6 (wild-type) mice showed only mild myocarditis, including normal survival postinfection with coxsackievirus group B serotype 3 (CVB3), infection of TRIF−/− mice led to the induction of cardiac remodeling, severe heart failure, and 100% mortality (p < 0.0001). These mice showed markedly reduced virus control in cardiac tissues and cardiomyocytes. This was accompained with dynamic cardiac cytokine activation in the heart, including a suppression of the antiviral cytokine IFN-β in the early viremic phase. TRIF−/− myocytes displayed a TLR4-dependent suppression of IFN-β, and pharmacological treatment of CVB3-infected TRIF−/− mice with murine IFN-β led to improved virus control and reduced cardiac inflammation. Additionally, this treatment within the viremic phase of myocarditis showed a significant long-term outcome indexed by reduced mortality (20 versus 100%; p < 0.001). TRIF is essential toward a cardioprotection against CVB3 infection.

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Protective Role for Interferon-β in Coxsackievirus B3 Infection

Cited by 151 publications

References 20 publications

Antigen‐presentation capacity of dendritic cells is impaired in ongoing enterovirus myocarditis

Antigen‐presentation capacity of dendritic cells is impaired in ongoing enterovirus myocarditis

Complex genetic control of host susceptibility to coxsackievirus B3-induced myocarditis

TRIF Is a Critical Survival Factor in Viral Cardiomyopathy

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