The replication of certain Coxsackie B virus strains in CHO cells.

Cell surface molecules that can act as viral receptors may exert an important selective pressure on RNA viral quasi-species. Coxsackie-Adenovirus Receptor and Decay Accelerating Factor (DAF, CD55) have been identified as receptors for Coxsackie B virus. In studies of viral replication using different strains of Coxsackievirus serotype 4 (CBV-4), it was found that despite lack of expression of these cell surface molecules on Chinese Hamster Ovary (CHO) cells and despite their common use as negative controls in Coxsackie B virus receptor assays, two strains were able to replicate, one (V89-4557) without cytopathic effect (CPE), and the other (T318) with strong CPE.

Tissue culture of isolated human pancreatic islets infected with different strains of coxsackievirus B4: assessment of virus replication and effects on islet morphology and insulin release.

The aim was to study whether different strains of Coxsackievirus B4 (CBV-4) are able to infect human pancreatic islet cells in vitro and cause morphological and functional damages. Isolated islets maintained in tissue culture were infected with five well- characterised strains of CBV-4. Aliquots of the culture medium were analysed with regard to virus replication and insulin content.

Differences in inhibition of replication between Coxsackie B4 virus strains in various cell lines by antibodies to some cell surface proteins.

Monoclonal antibodies that interact with the decay accelerating factor (DAF, CD55), the lymphocyte homing receptor (CD44) or the intercellular adhesion molecule I (ICAM- 1) were found to inhibit the replication of different strains of Coxsackievirus serotype B4 (CBV-4) to various extent. By adding antibodies to CD55 the replication of two (V345 and VD2921) of seven strains in HeLa cells, three (V89-4557, VD2921 and T318) of seven in A549-10C cells and one (VD2921) of five strains in RD cells was blocked totally. Consequently, the replication of one strain (VD2921) was blocked in all cells indicating that this strain uses CD55 as a receptor or as a co-receptor on all cell lines and is unable to use another cell surface protein.

Persistence of coxsackievirus B4 infection in rhabdomyosarcoma cells for 30 months. Brief report.

A persistent infection of rhabdomyosarcoma (RD) cells by Coxsackie B4 virus (CBV-4) was established. The persistently infected RD (piRD) cells have been maintained for over 130 passages (30 months) and have released virus continuously without cellular destruction. The production of infectious virus declined three times during the study.

Antibody responses to different strains of coxsackie B4 virus in patients with newly diagnosed type I diabetes mellitus or aseptic meningitis.

Considerable differences in antibody responses measured by capture-IgM RIA and neutralization tests (NT) were seen in children with newly diagnosed type I (insulin-dependent) diabetes mellitus (IDDM) when five different strains of Coxsackie B4 virus (CBV-4) were used. The IgM positivity of the 160 patients varied between 3.7 and 10.

Indications that maternal coxsackie B virus infection during pregnancy is a risk factor for childhood-onset IDDM.

In a population-based setting, we traced serum samples collected at time of birth from 55 mothers whose children later developed insulin-dependent diabetes (IDDM) and matched them pairwise to control subjects who gave birth at the same hospital during the same month. The sera were analysed for IgM antibodies to coxsackie B virus serotypes 2, 3 and 4 (CBV-2, 3 and 4) using a type-specific mu-antibody-capture radioimmunoassay. Despite a decreased power due to the close matching by time of birth we found a significantly higher frequency of CBV-3 IgM at delivery in mothers whose children later became diabetic compared to their matched control subjects.

Impaired Ca2+ response to glucose in mouse beta-cells infected with coxsackie B or Echo virus.

Five strains of Coxsackie B4 virus and one of Echo 11 virus were tested with regard to their ability to replicate in pancreatic mouse beta-cells and interfere with the alterations of the cytoplasmic Ca2+ concentration ([Ca2+]i) induced by glucose. All strains except one both multiplied and caused cytopathic effect. In a control group 68% of the beta-cells responded to 11 mM glucose with large amplitude oscillations of [Ca2+]i.

Coxsackie B virus infections in women with miscarriage.

To study the possible role of Coxsackie B virus serotypes 1-5 (CBV 1-5) as an etiological factor in miscarriage, 97 women with miscarriage were tested for the presence of CBV-IgM by radioimmunoassays (RIAs) and compared with 113 control women undergoing voluntary interruption of pregnancy in the same gestational week. Of the 80 women with miscarriage before the 13th week of gestation, 34 (42%) had CBV-IgM, whereas 18 of 100 (18%) corresponding control women had these antibodies, a statistically significant difference (P < 0.001).

High frequency of IgM antibodies to coxsackie B virus in sarcoidosis patients and patients with asbestos-related lesions.

By using radioimmunoassay (RIA) for detection of IgM antibodies to Coxsackie B viruses (CBV), the occurrence of these antibodies was investigated in patients with sarcoidosis and asbestos-related lesions. Sixty-one per cent of the patients with sarcoidosis, all patients with benign asbestos pleural effusion, and 67% of those with diffuse asbestos-related pleural thickening showed CBV-IgM. Patients with healed sarcoidosis or pleural plaques were all negative, and among the "healthy" controls seven per cent had CBV-IgM.

Increased frequency of coxsackie B virus IgM in women with spontaneous abortion.

IgM antibodies to Coxsackie B virus serotypes 1-5 (CBV 1-5) were studied by radioimmunoassay (RIA) of blood samples from women who had undergone a spontaneous abortion or given birth to a stillborn child. Results were compared with those of controls comprising healthy pregnant women who had not suffered such experiences. Among 48 women with abortions, 16 (33%) had CBV-IgM, while among the controls only three of 37 (8%) had these antibodies, a statistically significant difference (P less than 0.

Coxsackie B virus IgM in children at onset of type 1 (insulin-dependent) diabetes mellitus: evidence for IgM induction by a recent or current infection.

Thirty-five children with newly-diagnosed Type 1 (insulin-dependent) diabetes mellitus and their 47 siblings were investigated for the presence of IgM antibodies to Coxsackie B virus serotypes 1-5 (CBV 1-5) with the aid of mu-antibody-capture radioimmunoassays. When a high cut-off value was used, 16 (46%) diabetic children and 16 (34%) siblings showed CBV-IgM. Of the siblings of diabetic patients positive for CBV-IgM, 11 (44%) were CBV-IgM-positive; the corresponding figure for the siblings of negative patients was five (26%).

The possible role of Coxsackie A and echo viruses in the pathogenesis of type I diabetes mellitus studied by IgM analysis.

IgM antibodies to Coxsackie B virus (CBV) have recently been observed in the serum of a relatively high proportion of children with newly diagnosed insulin-dependent diabetes mellitus (IDDM). In the present study, 108 IDDM patients below the age of 15 years, diagnosed during the period 1976 to 1985, were investigated at the onset of their disease by mu-antibody-capture radioimmunoassay (RIA) of IgM against seven different enterovirus antigens, namely virions of CBV serotypes 1-5 (CBV 1-5) and procapsids of CBV 3 and CBV 5. As has been shown the RIAs with virions give type-specific or narrow type-specific reactions, whereas procapsids react with IgM against both homotypic and heterotypic enteroviruses.

Animal serum factor(s) causing adverse effects on RIAs of human enterovirus IgM.

The effects of animal sera used at various concentrations in dilution buffers for radioimmunoassays (RIAs) of human enterovirus-IgM were studied. The origin of the sera had no impact on the titres, but adverse effects on virus-specificity tests were noted when sera from some species were used. In attempts to block the binding of 35S-labelled virus by adding unlabelled virus, sera from cow, horse and lamb and from swine and man could usually not be used; instead of a blocking effect, an increase in bound labelled virus was noted in most cases.

The Swedish childhood diabetes study III: IgM against coxsackie B viruses in newly diagnosed type 1 (insulin-dependent) diabetic children--no evidence of increased antibody frequency.

Sera from essentially all Swedish children aged 0-14 years with Type 1 (insulin-dependent) diabetes mellitus with onset during an autumn period (October-December 1985) and a late spring period (May-June 1986) were selected. In all, 98 patients were analysed for IgM antibodies against coxsackie B virus serotypes 1 through 5 by a mu-antibody capture radio immunoassay technique. Sera from 94 referent children matched for age, sex and residential area, collected during the same period, were also analysed.

Antibodies against varicella-zoster virus and herpes simplex virus deoxythymidine kinase in heterologous infections.

Antibody responses to varicella-zoster virus (VZV) deoxythymidine kinase (dTK) and herpes simplex virus (HSV) dTK in homologous and heterologous infections were studied. Antibodies blocking the enzymatic activity of VZV-dTK appeared late after varicella and decreased more or less in parallel with the decreasing complement fixing [CF] titre. In herpes zoster, on the other hand, antibodies to VZV-dTK appeared soon after infection.

Enterovirus IgM detection: specificity of mu-antibody-capture radioimmunoassays using virions and procapsids of Coxsackie B virus.

A predominantly type-specific mu-capture radioimmunoassay (RIA) of IgM antibodies to Coxsackie B1-B5 (CB1-CB5) viruses was previously described (Frisk et al., 1984). The present study is concerned with the specificity of this assay, using as antigen different strains of one serotype (CB5) and procapsids of two serotypes (CB3 and CB5).

IgM against Coxsackie B viruses in children developing type I diabetes mellitus--a seven-year retrospective study.

IgM antibodies to coxsackievirus type B 1-5 (CB 1-5) have recently been observed in sera from children with newly diagnosed insulin-dependent diabetes mellitus (IDDM). In the present study IDDM patients below 15 years of age diagnosed between 1978 and 1984 inclusive in two different areas (counties) of Sweden, Uppsala and Linköping, were studied at the onset of their disease. The incidence of IDDM per 100,000 children below the age of 15 years varied between 11.

Matching of host genotype and serotypes of Coxsackie B virus in the development of juvenile diabetes.

Thirty-six consecutive paediatric patients (0-16 years old) with recently contracted juvenile diabetes (IDDM) during 1982-84 were included in the study. Sera were assayed for recent or current Coxsackie B virus (CBV) infection using a specific and sensitive IgM RIA. Eighteen patients (50%) had IgM against CBV 1-5.

High frequency of Coxsackie-B-virus-specific IgM in children developing type I diabetes during a period of high diabetes morbidity.

Twenty-four consecutive children with newly diagnosed insulin-dependent (type I) diabetes mellitus (IDDM) were investigated for a history of infectious disease. Thirteen of the 24 (54%) patients reported symptoms of acute infection within two months before diabetes was diagnosed. The mean age was 8.

An incidence peak of juvenile diabetes. Relation to Coxsackie B virus immune response.

All new cases of insulin dependent diabetes mellitus (IDDM) in children below 15 years of age were recorded prospectively during a 21-year period 1964-1984 in a defined uptake area with a relatively constant child population. The total number of children recorded was 222-111 boys and 111 girls. The number of new cases varied between 4 cases in 1968 and 20 in 1984; in 1983 seventeen new cases were recorded.

Application of an in vitro assay for serum thymidine kinase: results on viral disease and malignancies in humans.

An improved method for the detection of deoxythymidine kinase (TK) in human sera is reported. The method which utilizes 125I-iododeoxyuridine (IdUrd) as a substrate was used to measure TK in sera from patients with different diseases. Sera collected during the acute stage of infectious mononucleosis were found to contain elevated levels of TK, in most cases 10-40 times the normal value.

Indirect and reverse radioimmunoassays and their apparent specificities in the detection of antibodies to enteroviruses in human sera.

Indirect radioimmunoassays (RIAs) of IgM and IgG antibodies to enteroviruses have been developed, using coxsackieviruses B1 and B3, and echoviruses 11 and 30. The titres of IgM and IgG were assayed in paired sera from patients infected with one of these viruses or coxsackieviruses A7, A9, A16, B2, B4, B5 or echoviruses 4, 17, or 25. Both IgM and IgG were found in almost all serum pairs with each of the four viruses used as an antigen, and there were no certain differences between titres obtained with homologous and heterologous antigens.

Reverse radioimmunoassays of IgM and IgG antibodies to Coxsackie B viruses in patients with acute myopericarditis.

A reverse radioimmunoassay (RIA) of antibodies to enteroviruses, previously developed for the detection of IgM antibodies to Coxsackie B1 (CB1) and B3 (CB3) and to Echo 11 (E11) and 30 (E30) viruses, was extended in the present study for the detection of IgM antibodies to Coxsackie B2 (CB2), B4 (CB4), and B5 (CB5) viruses and of IgG antibodies to CB1-CB5, E11, and E30 viruses. After standardisation of the assays and application to a collection of serum specimens from patients with proven enterovirus infections, specimens from patients with diagnosed or suspected acute myo- and/or pericarditis (myopericarditis group), and control specimens from patients with nonenterovirus infections, were studied, as well as from apparently healthy subjects. Of the patients with enterovirus infections, 29 of 30 (97%) were positive in the IgM RIA and 19 of 25 (76%) in the IgG RIA.

False RIA IgM titres to herpes simplex virus and cytomegalovirus: factors causing them, and their absorption by protein A-Sepharose/IgG-protein A-Sepharose.

A method for the absorption of false radioimmunoassay (RIA) IgM titres against herpes simplex virus (HSV) and cytomegalovirus (CMV) is presented. The serum specimens were absorbed by a mixture of protein A-Sepharose and protein A-Sepharose saturated with normal human gamma globulin (PAS/IgG). The detection of rheumatoid factor of IgM class (IgM-RF) as well as antinuclear antibodies (ANA) of both IgM and IgG class by solid-phase RIA is also described, and their role in the false IgM results was studied.