Roles of the Humoral Response in Coxsackievirus B-Induced Disease

Gauntt, Charles J.

doi:10.1007/978-3-642-60687-8_12

Cited by 22 publications

(27 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation, which obscures a simple definition of a diabetogenic CVB phenotype, is consistent with CVB diabetogenicity being modulated by the host environment. The impact of the host environment on viral replication is well-established: expression of CVB phenotypes are modulated by a variety of influences, including immune status, age, strain, and gender of the mouse host (14,23,25,49,50).To test the hypothesis whether diabetogenicity is a common phenotype, we used a well-characterized, poorly pathogenic CVB3 strain, CVB3/GA (33,55,56), reasoning that rapid T1D onset should not be observed if the virus lacks a putative …”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Group B Coxsackievirus Diabetogenic Phenotype Correlates with Replication Efficiency

Kanno

Kim

Kono

et al. 2006

J Virol

View full text Add to dashboard Cite

Group B coxsackieviruses can initiate rapid onset type 1 diabetes (T1D) in old nonobese diabetic (NOD) mice. Inoculating high doses of poorly pathogenic CVB3/GA per mouse initiated rapid onset T1D. Viral protein was detectable in islets shortly after inoculation in association with beta cells as well as other primary islet cell types. The virulent strain CVB3/28 replicated to higher titers more rapidly than CVB3/GA in the pancreas and in established beta cell cultures. Exchange of 5-nontranslated regions between the two CVB3 strains demonstrated a variable impact on replication in beta cell cultures and suppression of in vivo replication for both strains. While any CVB strain may be able to induce T1D in prediabetic NOD mice, T1D onset is linked both to the viral replication rate and infectious dose.Insulin-dependent (type 1) diabetes mellitus (T1D) is an autoimmune, largely T-cell-mediated disease typically diagnosed before the end of the teen years (5, 6). A predisposing, multigenic component has been described but accounts for fewer than 50% of cases (7,35,45); environmental factors (e.g., viral infections) have therefore been proposed to explain the remaining cases of T1D (3,6,32,57,58) that cannot be ascribed solely to host-driven pathogenic autoimmunity. Human enterovirus (HEV) infections have long been suspected as environmental triggers of human T1D (12,22,27); infections by common HEVs, such as the group B coxsackieviruses (CVB 1 to 6) and diverse echoviruses, have been implicated as triggers of T1D onset at the time of or shortly after infection (8,9,13,19,28,37,39,40,42,52,60). Nonetheless, it remains unclear whether HEV initiates T1D in humans (18,21,24,26); evidence supporting an etiologic connection between HEV infection and T1D onset is not as well-established as the links between, for example, specific HEV infections and poliomyelitis, aseptic meningitis, or myocarditis (43).The nonobese diabetic (NOD) mouse is widely used as a model for the study of T1D. Previous work demonstrated that CVB inoculation protects young NOD mice significantly better from T1D as they age than no treatment (mock infected) (55). Unlike all other treatments that protect NOD mice from T1D (reviewed in references 4 and 46), the CVB are widely thought to be instigators of T1D onset with no protective effect. The extent of protection from T1D onset correlates directly with replication efficiency of the specific CVB strain that is employed: CVB strains that replicate to higher titers protect more mice than do CVB strains which replicate to lower titers. As NOD mice age, naturally occurring, pathogenic autoimmune insulitis develops rapidly (4) with widespread islet inflammation (insulitis) present by week 12 to 15 of age, when T1D also begins to occur. T1D rapidly ensues following inoculation of old (Ͼ12 weeks of age) NOD mice with virulent CVB (14), a model that recapitulates observations of sudden T1D onset in humans reported to occur during or shortly after an infection (37, 52). Initiation of rapid T1D onset in older mice...

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Group B Coxsackievirus Diabetogenic Phenotype Correlates with Replication Efficiency

Kanno

Kim

Kono

et al. 2006

J Virol

View full text Add to dashboard Cite

show abstract

“…The humoral response is a significant component of myocarditis in humans and in animal models (50,51), but its relationship to tissue injury is unclear. Both wild-type and apoJ-deficient mice developed similar and robust primary antimyosin Ab response, as well as frequent occurrence of Ab responses against other cardiac antigens.…”

Section: Figurementioning

confidence: 99%

Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis

McLaughlin¹,

Zhu²,

Mistry³

et al. 2000

J. Clin. Invest.

191

154

View full text Add to dashboard Cite

“…Another view is that coxsackieviruses cause chronic disease via immunemediated mechanisms directed against self-antigens. In mouse models, extensive evidence indicates that immunopathological mechanisms contribute to coxsackievirus-induced chronic disease (11,15,16,32,35,36).We have developed a mouse model of coxsackievirus B4-induced disease by using two serologically indistinguishable variants of the B4 serotype, CVB4-P and CVB4-V (5). The avirulent CVB4-P variant induces a mild, transient inflammation of the pancreas (pancreatitis) with full recovery of the tissues by 10 days of infection.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Exogenous Interleukin-12 Protects against Lethal Infection with Coxsackievirus B4

Potvin

Metzger

Lee

et al. 2003

J Virol

View full text Add to dashboard Cite

Infections with the group B coxsackieviruses either can be asymptomatic or can lead to debilitating chronic diseases. To elucidate the mechanism by which these viruses cause chronic disease, we developed a mouse model of chronic pancreatitis by using a virulent variant of coxsackievirus B4, CVB4-V. Infection with CVB4-V results in an early, severe pancreatitis, which can lead to mortality or progress to chronic pancreatitis. Chronic pancreatitis, in this model, is due to immunopathological mechanisms. We investigated whether interleukin-12 (IL-12) could modulate the outcome of CVB4-V infection. Eighty-five percent of the infected mice treated with 500 ng of IL-12 survived, whereas all untreated mice succumbed. To understand the mechanism underlying the beneficial effect of IL-12, we investigated the role of gamma interferon (IFN-␥). Three lines of evidence suggest that the protective effect of IL-12 is due to IFN-␥. The group B coxsackieviruses are enteroviruses belonging to the Picornaviridae family. In humans, most infections with the group B viruses are asymptomatic (25, 30). Generally, symptomatic infections result in mild illnesses of the upper respiratory tract, the gastrointestinal tract, and the skin. Occasionally, the group B coxsackieviruses cause chronic inflammatory disease of the pancreas (insulin-dependent type I diabetes mellitus, idiopathic chronic pancreatitis), heart (dilated cardiomyopathy), and central nervous system (7). The mechanism by which the group B viruses cause chronic disease is a topic of ongoing debate. One view is that coxsackieviruses cause chronic disease via viral persistence (18,19,38,40). Viral persistence may be due to the prolonged presence of low levels of infectious virus that continue to cause tissue injury. Alternatively, viral persistence may be due to the prolonged presence of viral RNA in the absence of infectious virus. The implication is that a low level of translation results in the synthesis of viral proteins that continue to stimulate immune responses, which cause prolonged tissue destruction. Another view is that coxsackieviruses cause chronic disease via immunemediated mechanisms directed against self-antigens. In mouse models, extensive evidence indicates that immunopathological mechanisms contribute to coxsackievirus-induced chronic disease (11,15,16,32,35,36).We have developed a mouse model of coxsackievirus B4-induced disease by using two serologically indistinguishable variants of the B4 serotype, CVB4-P and CVB4-V (5). The avirulent CVB4-P variant induces a mild, transient inflammation of the pancreas (pancreatitis) with full recovery of the tissues by 10 days of infection. The virulent CVB4-V variant induces a severe pancreatitis, which can lead to mortality or progress to chronic disease (chronic pancreatitis). We have shown that the severity of CVB4-V-induced chronic disease is influenced by the major histocompatibility complex (31), cytokines (33), and T cells (33). Chronic pancreatitis, in this model, is due to immunopathological mechanisms.Given t...

show abstract

Roles of the Humoral Response in Coxsackievirus B-Induced Disease

Cited by 22 publications

References 132 publications

Group B Coxsackievirus Diabetogenic Phenotype Correlates with Replication Efficiency

Group B Coxsackievirus Diabetogenic Phenotype Correlates with Replication Efficiency

Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis

Exogenous Interleukin-12 Protects against Lethal Infection with Coxsackievirus B4

Contact Info

Product

Resources

About