Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Coxsackievirus B4”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2003

A fatal case of coxsackievirus B4 meningoencephalitis.

BACKGROUND: Coxsackieviruses and echoviruses are common causes of aseptic meningitis, but they rarely cause life-threatening illness. We report a fatal case of coxsackievirus B4 meningoencephalitis in a woman who developed extrapyramidal symptoms suggestive of encephalitis lethargica. The exact causative agent of encephalitis lethargica has rarely been found, but most cases of the syndrome are assumed to be of viral origin. CASE DESCRIPTION: A 33-year-old woman previously treated with methylprednisolone and cyclophosphamide for Henoch-Schönlein purpura was transferred from a referring hospital because of sore throat, fever, and chills. Her neurologic findings progressed from headache with mild photophobia to lethargy, cogwheeling, increased tone in all 4 limbs, and brisk reflexes. The patient was diagnosed as having coxsackievirus B4 meningoencephalitis and, despite treatment with the experimental antiviral agent pleconaril, died of an overwhelming central nervous system infection and myocarditis. Magnetic resonance imaging showed focal hyperintense lesions in the substantia nigra that corresponded to the location of pathological changes seen at autopsy. CONCLUSIONS: This patient had a fulminant coxsackievirus B4 viral meningoencephalitis with a clinical pattern reminiscent of encephalitis lethargica and striking focal abnormalities in the substantia nigra identified on magnetic resonance imaging. The magnetic resonance imaging findings correlated with pathological changes identified at autopsy that were similar to the pathological findings observed in patients with encephalitis lethargica and postencephalitic parkinsonism. It is likely that the patient's immunocompromised state led to an overwhelming infection from an otherwise relatively innocuous viral infection.

Adult↗
PubMed1984

Pathogenicity of newly isolated coxsackievirus B4 for mouse pancreas.

Coxsackievirus B4 fresh isolates from patients with upper respiratory illness and aseptic meningitis were studied for their pathogenicity in the pancreas of SJL/J mice. Out of 12 virus isolates, 7 induced hypoglycaemia in mice 2 to 4 days after virus inoculation. All 3 isolates from faeces of patients induced hypoglycaemia in contrast to 3 viruses isolated from the cerebrospinal fluid which did not. Six isolates from throat swabs were either pathogenic (4 isolates) or non-pathogenic (2 isolates). It is concluded that at least two biologically distinct coxsackieviruses B4 prevail among humans.

Animals↗
PubMed2000

A point mutation in VP1 of coxsackievirus B4 alters antigenicity.

While coxsackievirus infections have been linked to several autoimmune diseases, very little is known about the immunogenicity of the coxsackieviruses. Using two genetically related variants of coxsackievirus B4, CB4-P and CB4-V, the relationship between virulence and antigenicity was examined. The virulent variant, CB4-V, was shown to be more antigenic than the avirulent CB4-P variant. The increased antigenicity of CB4-V was due to a single amino acid substitution in the VP1 capsid protein (a threonine residue at amino acid position 129), a site that had been previously identified as a major determinant of viral virulence. Thr-129 of VP1 is predicted to lie within a conformational B cell epitope. In addition, a nearby linear B cell epitope spanning residues 68 to 82 of VP1 was identified as a potential serotype-specific, neutralization antigenic site. The linear and conformational B cell epitopes of coxsackievirus B4 may be analogous to antigenic sites 1 and 1B of poliovirus. To address whether the increased antigenicity of CB4-V influenced the severity of disease, mouse strains that differ in their outcome to viral infection were analyzed. Mice that developed the most severe disease and succumbed to infection were more immunoresponsive than mice that survived infection with CB4-V. The data suggest that immune-mediated mechanisms play a role in the severity of CB4-V induced disease.

Amino Acid Sequence↗
PubMed1991

Molecular cloning of a heart antigen that cross-reacts with a neutralizing antibody to Coxsackievirus B4.

A panel of coxsackievirus B4 (CVB4) neutralizing monoclonal antibodies was tested against a panel of normal mouse tissues. One mAb, 356-1, reacted specifically with murine heart tissue. Examination of the reactivity of 356-1 with CVB4 polypeptides using Western immunoblotting revealed that 356-1 binds to the VP-1 capsid protein. Immunohistochemical studies revealed an A band pattern of staining of the heart by this antibody. Western immunoblotting of sequential differential extracts of heart showed that 356-1 predominantly reacted with the murine cardiac myosin heavy chain. A rather weak cross-reaction was found with actin. These observations were confirmed by the binding of 356-1 to purified cardiac myosin and actin. This antibody showed a higher affinity for murine cardiac muscle myosin than for skeletal muscle myosin. The monoclonal antibody 356-1 was then used to screen a lambda gt11 CD1 mouse heart cDNA expression library. Forty-eight positive plaques were obtained, 14 of which reacted strongly with the antibody and were selected for additional studies. In 13/14 clones, inserts were amplified using the polymerase chain reaction (PCR). The PCR products ranged in size from approximately 150 to 1400 bp. Northern hybridization using these inserts demonstrated that 10/13 recognized a approximately 6.5 kb message in mouse heart total RNA and not in liver total RNA. These amplified inserts were sequenced and were found to contain sequences which encode approximately 1/3 of the amino-terminal end of light meromyosin. By comparison with known sequences of rat alpha and beta cardiac myosin heavy chains, we were able to identify sequences specific for alpha chain as potential cross-reactive autoantigenic epitope.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Persistent infection of human thymic epithelial cells by coxsackievirus B4.

Persistent replication of coxsackievirus B4 (CVB4) E2 (diabetogenic) and CVB4 JBV (nondiabetogenic) strains in thymic epithelial cell (TEC)-enriched cultures (>or=95%) was proved by detection of positive- and negative-strand viral RNA by reverse transcription-PCR in extracted RNA from cell cultures, VP1 capsid protein detection by immunofluorescence (IF) staining, and release of infectious particles up to 30 days after infection without obvious cytolysis. By double-IF staining, cytokeratin-containing cells were shown to be susceptible to CVB4. The persistence of CVB4 was associated with a significantly increased rate of TEC proliferation (up to 70%) after 20 days of culture and a significantly increased chronic production of immunoreactive interleukin-6 (IL-6), leukemia inhibitory factor, and granulocyte-macrophage colony-stimulating factor in supernatant after 3 days of culture. The CVB4 replication and the release of cytokines were not restricted to the CVB4 E2 diabetogenic strain and did not depend on the genetic background of the host; however, TEC were more responsive to CVB4 E2 than CVB4 JBV as far as the production of cytokines.

Cell Division↗
PubMed1985

Neutralization kinetic analysis of echovirus 30 and coxsackievirus B4 strains revealed little antigenic variation amongst the echovirus strains.

An antigenic analysis was made of echovirus 30 and coxsackievirus B4 isolates by determining neutralization rate constants in neutralization kinetic tests. The seven echovirus 30 isolates included the prototype strain and six others isolated in Melbourne, Australia, between 1959 and 1982. Little antigenic heterogeneity was observed in contrast to the evidence of antigenic variation recorded in similar tests on seven coxsackievirus B4 isolates. These isolates also included the prototype strain, as well as six others isolated in Melbourne between 1958 and 1973. The results obtained with the coxsackievirus B4 isolates were in keeping with those observed particularly with the polioviruses and also coxsackievirus B4 by other workers. Those obtained with the echovirus 30 isolates were unexpected, as this virus is also a member of the enterovirus group.

Antigens, Viral↗
PubMed1985

Fatal coxsackievirus B4 infection in a neonate.

We reported a fatal coxsackievirus B4 infection in a neonate. The CSF WBC was elevated, with polymorphonuclear leukocytes predominating initially and lymphocytes predominating later in the illness. Autopsy findings included inflammation of the heart and liver. Coxsackievirus B4 was isolated from the heart and quantitated as 10(3) 50% tissue culture infectious doses (TCID50) per gram of myocardium.

Coxsackievirus Infections↗
PubMed1985

Detection of conserved and nonconserved epitopes on Coxsackievirus B4: frequency of antigenic change.

A sensitive microneutralization assay was used to detect antigenic variants of Coxsackievirus B4. Analysis of 47 clinical isolates with 16 monoclonal neutralizing antibodies revealed highly conserved, moderately conserved, and poorly conserved epitopes. Upon passage of Coxsackievirus B4 in tissue culture, certain epitopes disappeared and others appeared in the apparent absence of selective pressure. Changes in epitopes often exceeded a frequency of 10(-2). Despite considerable variation in individual epitopes, the overall antigenic composition of Coxsackievirus B4, as measured by the capacity of hyperimmune serum to neutralize clinical isolates, remains fairly constant.

Antibodies, Monoclonal↗
PubMed1983

Coxsackievirus B4: in vitro genetic markers and virulence.

The relationship of virulence to mice of the coxsackievirus B4 prototype JBV strain and selected mutants to several in vitro genetic markers has been examined. Markers studied include the t, d, DS, DEAE-D, and guanidine resistance (G), markers and a plaque size marker, here designated PS. The JVB strain was found to have the characteristics t-, d-, DS+, DEAE-D+, G-, PS+ and to be virulent when inoculated by the intraperitoneal route into suckling CD-1 mice (log titer/LD50 = 6.4/6.0). One naturally occurring mutant strain (characteristic = t-, d+, DS+, G-, PS+ was selected by terminal end point dilution and found to be virulent (log titer/LD50 = 7.0/6.0). Passage of the JVB population in the presence of guanidine hydrochloride (75 micrograms/ml) allowed selection of avirulent, guanidine resistant mutants with characteristics of t-, d-, DS+, DEAE-D+, G+. These mutants produced only small plaques (1.0-1.6 mm) and were designated PS-. The prototype and other selected strains that contained both large plaque and small plaque variants were characterized as PS+ and were invariably virulent. Although a variance in the d character has been demonstrated in some of the above strains, we conclude that virulence and the in vitro genetic markers t, d, DS, and DEAE-D are not related in our coxsackievirus B4 CD-1 mouse system. A relationship between plaque size (PS) and/or guanidine resistance (G+) of selected strains of coxsackievirus B4 and avirulence has been demonstrated in this system.

Animals↗
PubMed1990

Enhancement of coxsackievirus B4 virulence by indomethacin.

The safety of nonsteroidal anti-inflammatory agents in viral infections was assessed in a mouse model of coxsackievirus B4 neonatal myocarditis. Two-day-old mice were infected intraperitoneally with 10(4) TCID50 coxsackievirus B4 and then randomized to receive indomethacin or saline for 7 days. A number of them were killed on designated days. Mortality, viral titers, antibody, and interferon levels plus histopathologic changes in the heart were compared. Among treated animals, mortality was greater (22/45 vs 7/27; p = 0.07) and viral titers were higher on days 4 and 7 (p = 0.038 and 0.028, respectively). Interferon levels were lower on days 4 and 7 (p = 0.028 and 0.008, respectively), and histopathologic changes were more extensive on days 7 and 21 (p = 0.008 and 0.028, respectively). These findings show that indomethacin decreased interferon production, increased coxsackievirus4 titers, and enhanced the virulence of coxsackievirus B4. These results raise significant concerns about the safety of indiscriminate use of nonsteroidal anti-inflammatory agents during severe viral infections.

Animals↗
PubMed1992

Focal ventricular thinning caused by indomethacin in the late phase of coxsackievirus B4 murine myocarditis.

Indomethacin has been shown to increase virus titers and to worsen cardiac injury in the acute phase of coxsackievirus B4 murine myocarditis. The authors evaluated the effects of indomethacin on the histopathologic changes in a later phase of this disease after virus clearance. Two-day old CD1 mice were infected with coxsackievirus B4. Ten days later, surviving animals were randomized to receive indomethacin or saline intraperitoneally for 10 days. They were then euthanatized, and their hearts were examined for the presence of inflammation, necrosis, scarring, and focal thinning. Mortality was slightly higher among treated animals (7/15 versus 2/12, p = 0.3). The index of inflammation (0.6 +/- 0.5 versus 0.7 +/- 0.5) necrosis and scarring (0.4 +/- 0.5 versus 0.3 +/- 0.5) among treated and control animals, respectively, was not significantly different, but the size of involved myocardium (149742 +/- 201982 versus 35300 +/- 45413 microns2) was remarkably larger (p less than 0.05), and focal ventricular thinning (5/12 versus 0/10, p = 0.03) was encountered among indomethacin recipients exclusively. These findings indicate that indomethacin treatment in the late phase of coxsackievirus B4 myocarditis enhances myocardial damage and increases the incidence of focal ventricular thinning.

Animals↗
PubMed2003

Exogenous interleukin-12 protects against lethal infection with coxsackievirus B4.

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-gamma). Three lines of evidence suggest that the protective effect of IL-12 is due to IFN-gamma. First, administration of IL-12 increased the production of endogenous IFN-gamma in CVB4-V-infected mice. Both NK and NKT cells were identified as the source of IFN-gamma. Second, IFN-gamma knockout mice treated with IL-12 succumbed to infection with CVB4-V. Third, wild-type mice treated with IFN-gamma survived infection with CVB4-V. Due to the antiviral effects of IFN-gamma, we examined whether IL-12 treatment affected viral replication. Administration of IL-12 did not decrease viral replication in the pancreas, but it did prevent extensive tissue damage and the subsequent development of chronic pancreatitis. The data suggest that IL-12 treatment during CVB4-V infection is able to suppress the immunopathological mechanisms that lead to chronic disease.

Animals↗
PubMed1986

Anti-idiotypic antibodies to monoclonal antibodies that neutralize coxsackievirus B4 do not recognize viral receptors.

We have made anti-idiotypic antibodies in rabbits against three mouse monoclonal neutralizing antibodies with specificities for independent epitopes on Coxsackievirus B4. Each of these anti-idiotypic antibodies was found to react specifically with the immunizing monoclonal antibody in radioimmunoassays and did not react with the other monoclonal antibodies. In addition, the anti-idiotypic antibodies specifically inhibited the function (i.e., virus neutralization) of the immunizing antibody. These anti-idiotypic antibodies were tested for their ability to recognize receptors for Coxsackievirus B4 as measured by their ability to inhibit the attachment of radiolabeled virus to cellular receptors. The anti-idiotypic antibodies did not block the binding of Coxsackievirus B4 to monkey kidney cells. Moreover, when tested for their ability to bind to other receptor positive cells, none of the anti-idiotypic antibodies bound above control levels. Anti-idiotypic antibodies did induce a small anti-anti-idiotypic antibody response in mice when tested by radioimmunoassay; however, little if any virus neutralizing activity was found in the sera of these mice. Our results contrast to those reported for anti-idiotypic antibodies in several other virus systems and suggest that not all anti-idiotypic antibodies made against neutralizing antibodies are capable of eliciting an antiviral immune response or binding to viral viral receptors on cells.

Animals↗
PubMed1978

Coxsackievirus B4 myocarditis in mice: valvular changes in virus-infected and control animals.

Suckling, weanling, and adult HaM/ICR and Swiss-Webster mice were inoculated intraperitoneally with the TC631 and Dowell strains of coxsackievirus B4. Vero cell-inoculated and uninoculated control mice were also studied under code. An intense, necrotizing myopericarditis was produced in suckling mice; it was less severe in weanlings. Myocarditis did not occur when coxsackievirus B4 was inoculated into adult mice. Progressive sclerosis and thickening of all valves in both strains of mice were observed with equal frequency in infected and control mice. There was no evidence that coxsackievirus B4 induced a specific valvular or endocardial lesion.

Animals↗
PubMed2003

Lack of islet neogenesis plays a key role in beta-cell depletion in mice infected with a diabetogenic variant of coxsackievirus B4.

Group B coxsackieviruses (CVBs) have a well-established association with type 1 diabetes but the mechanism of depletion of beta-cell mass following infection has not yet been defined. In this report we show that the major difference in pathogenesis between the E2 diabetogenic strain of CVB4 and the prototypic JVB strain in SJL mice is not in tropism for islet cells but in the degree of damage inflicted on the exocrine pancreas and the resulting capacity for regeneration of both acinar and islet tissue by the host. Both strains replicated to a high titre in acinar tissue up to day 3 post-infection (p.i.), while the islets of Langerhans were largely spared. However, the pancreas in the JVB-infected animals then regenerated and many small islets were seen throughout the tissue by day 10 p.i. In contrast, the acinar tissue in E2-infected mice became increasingly necrotic until all that remained by day 21 p.i. were large islets containing varying numbers of dead cells, caught up in strands of connective tissue. Surviving beta cells were found to synthesize little insulin, although islet amyloid polypeptide was detected and glucagon synthesis in alpha cells appeared normal or enhanced. Our results suggest that the key to CVB-E2-induced damage lies in the exocrine tissue and prevention of islet neogenesis rather than from direct effects on existing islets.

Animals↗
PubMed1994

Characterization of the N-terminal part of the neutralizing antigenic site I of coxsackievirus B4 by mutation analysis of antigen chimeras.

Coxsackievirus B3 (CVB3) as a potential RNA virus vector for the presentation of foreign antigenic epitopes was further characterized. Insertion mutagenesis of infectious CVB3 cDNA yielded viable antigen chimeras containing variant BC loops of VP1 of coxsackievirus B4 (CVB4). Analysis of three antigen chimeras allowed the mapping of the N-terminal part of the neutralizing antigenic site 1 (N-Ag1) of CVB4 which is located in the BC loop of the structural protein VP1. A significant neutralization of a viable chimera with the deletion of CVB4-specific amino acid Ser-83 at the amino terminus of the VP1 BC loop was obtained with CVB4 serotype-specific polyclonal antisera. This neutralization was reduced after further deletion of the adjacent Ala-84, suggesting that this amino acid either constitutes the beginning of N-Ag1 of CVB4 or is essential for the conformation of the adjacent epitope. In contrast, exchange of amino acid Ser-86 to alanine, in the middle of the BC loop, led to complete loss of reactivity with CVB4-specific antibodies, demonstrating the importance of this residue for binding of CVB4 neutralizing antisera. Furthermore, we observed that manipulations of the VP1 BC loop resulted in increased thermolability of the viable chimeras in comparison to CVB3, although replication efficiencies were similar.

Amino Acid Sequence↗
PubMed1999

Coxsackievirus B4 as a cause of adult chorioretinitis.

PURPOSE: To describe the clinical manifestation and course of chorioretinitis presumed to be secondary to coxsackievirus infection in an adult. METHOD: Case report documented by fundus photography and fluorescein angiography. RESULTS: Ophthalmoscopic examination of a symptomatic 34-year-old woman showed several cream-colored parafoveal spots at the level of the retinal pigment epithelium and similar, multiple confluent spots in the midperiphery of both eyes. Titers for coxsackievirus B4 demonstrated a fourfold rise between acute and convalescent sera. CONCLUSION: Coxsackievirus B4 is apparently a rare cause of chorioretinitis but nevertheless should be considered in the appropriate clinical setting.

Administration, Oral↗
PubMed2001

No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children.

Enterovirus infections are a potential environmental trigger of the autoimmune process leading to clinical type 1 diabetes. It has been suggested that the risk of virus-induced beta-cell damage might be connected with a defect in humoral immune responsiveness to enteroviruses. In the present study we assessed whether such a defect in IgG responsiveness to coxsackievirus B4 antigen existed in young children who developed diabetes-associated autoantibodies during prospective observation from birth until the age of 18 months. IgG levels and maturation of antibody avidity were analysed in 21 children with autoantibodies and 41 control children who had experienced an equal number of enterovirus infections and were additionally matched for age, sex and HLA-DQB1 risk alleles for type 1 diabetes but had not produced diabetes-associated autoantibodies. IgG levels to coxsackievirus B4 were high in cord serum reflecting the presence of maternal antibodies. Mean IgG levels gradually decreased but began to increase after the age of 6 months, showing no significant difference between autoantibody positive and control children. The avidity of antibodies was strong in cord serum and decreased gradually during the first year of life when maternal antibodies disappeared. The avidity indices, which varied considerably from child to child, did not differ between the autoantibody-positive and -negative subjects. In conclusion, our data suggest that children affected by a beta-cell damaging autoimmune process show normal responses to coxsackievirus B4 antigens.

Antibodies, Viral↗