Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines

Anti-complement immunofluorescence (ACIF) was used to study the complementfixing antigens of human lymphoblastoid cell lines. These cell lines carry the Epstein-Barr virus (EBV) genome although only producer cultures synthetize EBV-specific antigens (virus capsid antigen, VCA and early antigen, EA) detectable by direct and indirect immunofluorescence, usually in less than 5% of the cells. The ACIF test revealed an antigen localized in the nucleus of the lymphoblastoid cells. In contrast to EA and VCA, this antigen was present in over 90% of the cells of both producer and non-producer cultures. The antigen was shown to be specific for EBV by comparing the reactions of 52 sera in the ACIF test. Sera giving the nuclear reaction contained antibodies to VCA, EA or antigens detectable by complement fixation tests on cell extracts, but sera without EBV antibodies failed to give the reaction. Weak, equivocal or discordant reactions occurred with six sera with low titres in VCA, EA or complement fixation tests. Cell lines derived by transformation of human and primate lymphocytes by EBV gave the nuclear reaction. Control cells with no known association with EBV were non-reactive. These included foetal lymphocytes transformed by phytohaemagglutinin, cell lines derived from breast cancer, glioma, normal glia, pleuritis maligna and myeloma, and two marmoset lymphoid lines carrying Herpesvirus saimiri (HVS). In preliminary experiments, the ACIF test was used as a tool to trace the EBV genome at the cellular level. Cells from two Burkitt lymphoma biopsies, one tested after biopsy and one after passaging in nude mice, contained an EBV-specific antigen. Three clones of cells derived from hybrids of mouse somatic cells and a human lymphoblastoid cell line also contained such an antigen, but the number of reactive cells varied from clone to clone. A fourth clone was non-reactive.     

Origin of lymphoid lines established from mixed cultures of cord-blood lymphocytes and explants from infectious mononucleosis, Burkitt lymphoma and healthy donors.

Lymphocytes were explanted from EBV-seropositive donors including peripheral blood of infectious mononucleosis patients, healthy donors and EBV-genome-carrying cells from Burkitt lymphoma (BL) biopsies or nude mouse-passaged, BL-biopsy-derived lines. The explanted cells were mixed with fresh cord-blood lymphocytes from mice of the opposite sex. In all categories of derived lines, cord-blood cell progeny was predominant, as judged by the sex marker and other associated markers. Only one BL biopsy line, serially passaged in nude mice, gave rise to a monoclonal lymphoma line.     

Early primary infection and high Epstein-barr virus antibody titers in greenland eskimos at high risk for nasopharyngeal carcinoma

In a comparative study of populations at high and low risk of nasopharyngeal carcinoma (NPC), sera from 442 Eskimo and 770 Danish children and adolescents were tested for the presence of antibodies against Epstein-Barr virus (EBV). Eskimo children in Greenland were seropositive at an early age and showed significantly higher titers of IgG antibody to the viral capsid antigen (VCA) (p<0.0001) and soluble (S) antigen (p<.005) than Danes matched for age and sex, but had similar levels of IgA antibody to VCA and IgG antibody to the early antigen (EA). The high geometric mean VCA (IgG) titers found in certain age groups of Eskimo children were as high as those previously reported from areas in Africa highly endemic for Burkitt's lymphoma. In Greenland, neither location nor household size was a determining factor for prevalence or titer of VCA (IgG). The high antibody titers among Eskimo children probably reflect exposure to a large inoculum of EBV at the time of primary infection, infection early in life and/or re-exposure due to the higher incidence of EBV infection in Greenland. In view of the high incidence of NPC in Greenland and the known association of this tumor with EBV, we speculate that the time and quantitative aspects of the primary infection are also factors of relevance in the etiology of NPC.     

The action of DNA antagonists on Epstein-Barr virus (EBV)-associated early antigen (EA) in Burkitt lymphoma lines

The effect of two DNA antagonists (IUDR and Ara C) on EBV-associated antigens was studied in two BL-derived carrier culture lines (P3HR-1 and Onesmas). Both drugs led to an accumulation of the early antigen (EA) from 2% in the untreated to 5–40% in the treated cultures. Ara C blocked the production of viral capsid antigen (VCA) whereas a small number of VCA + cells were still present after IUDR treatment. Reversion of Ara C-induced DNA inhibition led to the appearance of VCA + cells, reaching a higher level than in the untreated control samples. Combined immunofluorescence and autoradiography showed that the majority of VCA + cells incorporated H³-thymidine. These facts are in line with the hypothesis that EA can be made in the absence of cellular DNA synthesis, whereas VCA production is dependent on the DNA synthesis. The relationship between EA and two other EBV-associated antigens, MA (membrane antigen) and VCA (viral capsid antigen) was studied by the two-color immuno-fluorescence technique. VCA + cells were EA+ and MA+. EA + VCA - cells were partly MA + and partly MA-. This is in good agreement with the corresponding findings on the EBV-infected Raji cell system (Gergely et al., 1970a).     

Antibodies to epstein-barr virus-specific antigens in patients with hairy-cell leukemia

Antibody titers to Epstein-Barr virus (EBV)-specific antigens of 19 patients with hairy-cell leukemia (HCL) were markedly elevated. All patients showed high titers of IgG anti-viral capsid antigen (VCA) reactivity equal to or greater than 320 (reciprocal titer). The anti-VCA reciprocal geometric mean titer (GTM) was 1106 in contrast to a GMT of 80 for healthy controls (p < 0.001). No IgM anti-VCA antibody was detected, but three patients had IgA anti-VCA antibodies. Fourteen patients had elevated anti-early antigen (EA) titers (GMT = 177) which were indicative of active infections with EBV. Seven of the 14 patients demonstrated the diffuse component antibody of the early antigen (EA) complex at a GMT of 98. Anti-Epstein-Barr virus nuclear antigen (EBNA) was detected in sera of 16 patients (GMT = 64, controls GMT = 79). It is noteworthy that three patients with anti-VCA titers lacked anti-EBNA titers. These antibody responses suggest that immunodeficiency secondary to HCL allowed reactivation of the virus.     

Significance of Plasma IgA and IgG Antibodies to Epstein-Barr Virus Early and Viral Capsid Antigens in Thai Nasopharyngeal Carcinoma

Epstein-Barr virus (EBV) is an important causal factor of human nasopharyngeal carcinoma (NPC). High levels ‍of serum IgA and IgG antibodies to EBV early and viral capsid antigens (IgA/EA, IgA/VCA, IgG/EA and IgG/VCA) ‍have been reported in NPC patients. Since specific serum IgA/EA, IgA/VCA and IgG/EA are claimed to be useful ‍serological markers for NPC. In order to evaluate whether plasma IgA/EA, IgA/VCA, IgG/EA and IgG/VCA antibody ‍levels are useful markers for diagnosis and prognosis of Thai NPC, we examined the prevalence of these antibodies ‍in 79 NPC patients, and 127 age-matched controls (47 healthy subjects (HS), 32 cases of other disease (OD) and 48 ‍cases of other cancer (OC)) by using an indirect immunofluorescence assay. The prevalence of plasma IgA/EA, IgA/ ‍VCA, and IgG/EA in NPC patients (55.7, 68.4 and 68.4%) was significantly higher than in the HS (0.0, 0.0 and ‍20.5%,), OD (0.0, 0.0 and 3.1%) and OC (0.0, 0.0 and 20.8%) groups (p<0.05). The prevalence of plasma IgG/VCA ‍in NPC patients (93.7%) was significantly different from those for the OD and OC groups (71.9 and 43.8%) but not ‍for the HS group (89.4%). In NPC patients, the geometric mean titers (GMT) of plasma IgA/EA, IgA/VCA and IgG/ ‍EA were increased with an advanced clinical stage of disease but not IgG/VCA. In contrast, GMT of IgG/VCA was ‍increased with aggressive type of disease (histological type) but not IgA/EA, IgA/VCA, and IgG/VCA. The results of ‍our study suggest that plasma IgA/EA, IgA/VCA and IgG/EA antibodies may be useful markers for diagnosis and ‍assessing prognosis of Thai NPC. ‍     

EBV-associated serological patterns in a Burkitt lymphoma patient during regression and recurrence

Three serological reactions have been followed in a Burkitt lymphoma patient during the clinical course of the disease, including long-term regression, followed by recurrence and progressive growth, in spite of chemotherapy. Antibodies directed against surface antigens characteristic for EBV-carrying lymphoblastoid cell lines of Burkitt lymphoma origin were assessed by blocking of direct membrane immunofluorescence. The level of surface reactive antibodies was high while the patient was in long-term regression. It decreased to an insignificant level approximately half a year before tumor recurrence was clinically diagnosed. Immediately after the recurrence, it remained at a low level but increased subsequently and remained at a high level until the death of the patient. The anti-EBV antibody level itself showed only minor fluctuations. Precipitating antibodies, directed against soluble antigen extracted from the EBV-carrying Jijoye cell line, were absent during long-term regression. They appeared soon after recurrence and remained at a high level until the patient died. Repeated biopsy specimens were taken after the recurrence. In the course of progressive growth, a coating of the IgG type was seen to accumulate on the surface of the tumor cells. Possible implications of these findings are discussed.     

Induction of epstein-barr virus by a new tumor promoter,teleocidin, compared to induction by TPA

The effect of teleocidin, a new, naturally occurring tumor promoter, on induction of Epstein-Barr virus (EBV), was compared with that of a known tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Early antigen (EA) and/or capsid antigen (VCA) of EBV was induced in the EBV genome-carrying cell lines C-6 and P3HR-I cells by teleocidin, its effect being maximal at a concentration of 12.5 ng/ml. The production of infectious EBV from P3HR-I cells was enhanced by teleocidin maximally at a concentration of 0.5 to 2.5 ng/ml. The outgrowth of EBV-transformed cells from peripheral lymphocytes of seropositive healthy donors was also enhanced by teleocidin at a concentration of 0.02 to 0.5 ng/ml. TPA tested simultaneously in all experiments exhibited the same activities as teleocidin, and was effective at similar concentrations. Teleocidin enhanced both EA and VCA synthesis in P3HR-I cells additively with n-butyrate, but not with TPA. This suggests that teleocidin and TPA have a common mechanism of action, although their chemical structures are different.     

提高EB病毒血清学在诊断鼻咽癌中的效益

目的 探讨同时应用VCA-IgA,EA-IgA和EA-IgG三项检测在血清学诊断鼻咽癌中的效益。方法 收集266例未经治疗的鼻咽癌患者和347例健康成人的血清,用免疫酶法检测VCA-IgA,用酶联免疫吸附法（ELISA）替代免疫酶法检测EA-IgA和EA-IgG抗体。应用新的统计学方法来评估这三项检测的不同优势比。结果 同时应用VCA-IgA,EA-IgG和EA-IgA三项检测的灵敏度和特异度分别为95.11%和97.41%。高于这三项检测的单独应用（VCA-IgA为90.60%和94.52%,EA-IgG为93.98%和93.66,EA-IgA为89.84%和88.18%）,再者,VCA-IgA,EA-IgG和EA-IgA三项检测均呈阳性者的优势比（1912.5)远远高于其中两项检测呈阳性者（VCA-IgA和EA-IgG为27.9032,EA-IgG和EA-IgA为11.1690;VCA-IgA和EA-IgA为8.0328)。而两项检测阳性的优势比又高于单个检测阳性者（VCA-IgA为0.1214;EA-IgG为0.1705;EA-IgA为0.0488)。结论 ELISA法较免疫酶法更能确切反映血清中EB病毒早期抗原的抗体水平。VCA-IgA,EA-IgG和EA-IgA的联合应用能显著提高灵敏度和特异度,明显增高检测阳性的优势比,因此,能有效地提高EB病毒血清学在诊断鼻咽癌时的效益。     

Detection of the EBV-determined nuclear antigen (EBNA) in Burkitt's lymphoma and nasopharyngeal carcinoma biopsies by the acid fixed nuclear binding (AFNB) technique.

Epstein-Barr virus (EBV) carrying biopsies of Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC) were used to examine the question whether the EBV-associated nuclear antigen (EBNA) can be demonstrated by the acid fixed nuclear binding (AFNB) technique, developed previously for the demonstration of EBNA in cultured cell lines [11]. Extracts of 5 BL and 5 NPC biopsies gave a brilliant, EBNA specific fluorescence after binding to acid fixed chicken red cells. Similar extracts of 3 other African tumors that are not known to carry the EBV-genome were negative, in spite of the fact that they were derived from EBV-seropositive patients with relatively high anti-EBV (VCA) antibody titers. Crude extraction and DNA-cellulose purification gave equally active extracts, provided that incubation was carried out at 4 degrees C. These results show that the acid fixed nuclear binding technique can be applied to biopsy material. This may be helpful in searching for EBNA carrying cells in heterogeneous normal and tumor tissues in vivo where the direct in situ ACIF staining for EBNA is known to meet great difficulties.     

Mouse monoclonal antibody to embryonic antigen: development, cross-reactivity with rodent and human tumors, and preliminary polypeptide characterization

Hybridomas producing IgM and IgG monoclonal antibodies (MoAb) to embryonic or fetal antigens (EA) were obtained in a completely syngeneic system. Lethally irradiated, 13-day-gestation, C57BL/6N mouse fetal cells or KCI extracts of these fetal cells obtained from primaparous donors were used as immunogens in several regimens to induce splenocytes in C57BL/6N mice that were utilized to form the hybridomas following fusion with a mouse myeloma line. Successful growth and cloning of the IgM-producing hybridomas required supplementation with factor(s) produced in the growth medium of the macrophage cell line RAW 264.7. An enzyme-linked immunosorbent assay (ELISA) was employed to screen the primary fusion hybridomas for antibody directed against fetal cell or adult cell determinants with the use of freshly explanted tissues. Glutaraldehyde-fixed fetal cells as well as crude fetal cell membranes were used as EA+ target cells (i.e., cell lines known to activate T-lymphocyte-mediated tumor resistance) in a solid-phase ELISA to perform quantitative ELISA adsorption tests of the MoAb. The anti-EA monoclonal IgM and the IgG detected common, embryo-specific antigen(s) on mouse, hamster, and human fetuses. Term fetal cells and adult normal tissues of the mouse, hamster, and human did not express cross-reactive determinants for the MoAb by absorption analysis and/or by direct binding in ELISA. EA expression as oncofetal antigens could also be detected with the monoclones on several rodent tumor cell lines tested as well as on a variety of human carcinomas but not on a spectrum of normal human tissues with the use of indirect ELISA absorption and affinity gel and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses. Fluorescence analysis with the monoclones demonstrated specific reactivity with the surface of EA+ tumor cells in the FACS IV flow cytometer. The responsible antigen was carried on a 44- and a 200-kilodalton polypeptide.     

Prognostic value of serum Epstein–Barr virus antibodies in patients with nasopharyngeal carcinoma and undetectable pretreatment Epstein–Barr virus DNA

Epstein–Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum IgA antibodies against early antigen (EA‐IgA) and viral capsid antigen (VCA‐IgA) are the most commonly used to screen for NPC in endemic areas. However, the prognostic value of serum EA‐IgA and VCA‐IgA in patients with NPC is less clear. We hypothesize that serum EA‐IgA and VCA‐IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non‐metastatic NPC and undetectable pEBV DNA were included. Serum EA‐IgA and VCA‐IgA were determined by ELISA. After analysis, serum EA‐IgA and VCA‐IgA loads correlated positively with T, N, and overall stage (all P < 0.05). Serum EA‐IgA was not associated with survival outcome in univariable analyses. But patients with serum VCA‐IgA >1:120 had significantly inferior 5‐year progression‐free survival (80.4% vs 89.6%, P = 0.025), distant metastasis‐free survival (88.4% vs 94.8%, P = 0.050), and locoregional relapse‐free survival (88.4% vs 95.6%, P = 0.023; log–rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA‐IgA became insignificant. Further analyses revealed that serum VCA‐IgA was not an independent prognostic factor in early N (N0–1) or advanced N (N2–3) stage NPC. In summary, although both EA‐IgA and VCA‐IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA.     

Hybridization between a human epithelial line, infectable by Epstein-Barr virus, and Burkitt lymphoma lines: membrane properties, superinfectability, inducibility and tumorigenicity

The human epithelial line U, which is partially infectable with EBV, was hybridized with the EBV-genome carrying Burkitt lymphoma lines P3HR-1 and Daudi. Authenticity of the hybrids U-Put and U-Dut was established by isoenzyme studies. Although the two hybrids carried the EBV genome derived from the lymphoma parent, being 100% positive for Epstein-Barr-virus-associated nuclear antigen (EBNA), they resembled the U parent in many respects: they were deficient for membrane immunoglobulins and Fc receptors, and had a lower concentration of EBV-C3 receptors than either parent. Unlike the P3HR-1 parent, U-Put hybrid was nonpermissive for both the EBV cycle antigens, early antigen (EA) and viral capsid antigen (VCA). The inducing agent 12-O-tetra-decanoyl-phorbol-13-acetate (TPA) caused distinct viral early antigen synthesis (EA) in U-Put, lower, however, than that of the parental P3HR-1. U-Dut was completely nonpermissive and noninducible for early and viral capsid antigens. Thus, even an epithelial parent infectable by EBV restricted, although not completely, expression of EBV antigens, with the exception of EBNA. It has been suggested that EBNA is an autonomous function of the viral genome, independent of host cell control; the latter regulates expression of antigens related to viral cycle. The hybrids U-Put and U-Dut resembled the U parent also in regard to growth in soft agar and tumorigenicity in nude mice, although in this respect the lymphoma parental properties were not completely eclipsed.     

Nasopharyngeal carcinoma: significance of changes in Epstein-Barr virus-related antibody patterns following therapy.

Sera were collected at intervals of 3 to 8 months over a 4- to 5-year period from more than 103 patients with nasopharyngeal carcinomas (NPC) and examined for their spectra and titers of antibodies to Epstein-Barr virus (EBV)-related antigens. They were titrated for IgG, IgA and IgM antibodies to EB viral capsid antigen (VCA), for IgG and IgA antibodies to the D (diffuse) and R (restricted) components of the EBV-determined early antigen (EA) complex, and for antibodies to the EBV-associated nuclear antigen (EBNA). In the as yet untreated patients the incidences and titers of most of the antibodies increased with the stage of the disease; i.e., essentially with the total tumor burden. Such increases were observed in individual patients whose disease ultimately progressed to death, at times well in advance of the recognition of relapses or metastases. Increases were not noted or were only minor and delayed in some fatal cases if the tumor extended to the cranial cavity in the absence of significant involvement of cervical lymph nodes. In contrast, patients who responded well to therapy and remained clinically free of disease during the 4- or 5-year observation period after, at most, early minor relapses, showed gradual, steady declines in the titers of all antibodies except anti-EBNA. Thus, VCA-specific IgA and D-specific IgA and IgG became undetectable in time in many of the patients. In several long-term survivors the declines were arrested at given levels or a reversal to increasing titers was noted which was followed in time by detection of a recurrent tumor or metastases in some cases, but not in others who remain under close observation. It would appear that serologic monitoring of NPC patients may warn of recurrent tumor activity well before it becomes clinically evident.     

Immunofluorescence and anti-complement immunofluorescence absorption tests for quantitation of Epstein-Barr virus-associated antigens.

Immunofluorescence absorption methods are described which permit quantitative estimation and differentiation of Epstein-Barr virus (EBV)-associated antigens (virus capsid antigen, VCA, early antigen, EA and EBV-determined nuclear antigen, EBNA) in cell extracts. EBNA was present in all cell lines (producer and non-producer) which carried the EBV-genome, while VCA and EA were present in producer lines only. All the antigens were absent from a lymphoid cell line (MOLT-4) which lacked the EBV-genome, as well as from leukemia cells from peripheral blood. The techniques demonstrated antigenic identity of the various antigens when prepared from different cell lines.     

Lack of correlation between EBV serology and presence of EBV in the Hodgkin and Reed-Sternberg cells of patients with Hodgkin's disease

Epstein-Barr virus (EBV) is detected in Hodgkin and Reed-Sternberg (HRS) cells in up to 50% of patients with Hodgkin's disease (HD). HD patients have been reported to express high serum titers against EBV antigens, even prior to the diagnosis of HD. Patients with high serum titers have a poorer prognosis. The aim of this study was to examine the relationship between the presence of EBV in HRS cells and the antibody titers reactive with different EBV antigens. Frozen serum and histopathological tissues were available from 107 untreated HD patients diagnosed between 1979 and 1991. The presence of EBV in the HRS cells was evaluated with immunohistochemistry directed against the LMP-1 antigen and/or with in situ hybridization of EBER-1. Analyses were performed of serum titers against early antigen (EA), diffuse (IgA and IgG) and restricted (IgG), virus-capsid antigen (VCA) (IgA and IgG), and EBV-encoded nuclear antigens (EBNA, EBNA 1, EBNA 2A, EBNA 2B, EBNA 6). EBV was detected in 27/107 (25%) tumor specimens, with a higher proportion in the MC group 8/13 (62%) (p < 0.01). IgG VCA and EBNA were detected in 99/107 (93%), evidence of a previous EBV infection. There were no significant relationships between antibody titers reactive with different EBV antigens and detectable EBV in HRS cells. Furthermore, there did not appear to be any relationship between EBV serology or the presence of EBV in HRS cells and clinical outcome. The role of EBV in the development of HD, especially its relationship to the immunological response, remains unclear. Int. J. Cancer 72:394–397, 1997. © 1997 Wiley-Liss, Inc.     

Expression of the Epstein-Barr virus genome in a nasopharyngeal carcinoma epithelial tumor cell line

An epithelial tumor cell line was recently established from a biopsy specimen of a nasopharyngeal carcinoma (NPC), and designated HONE-I. Uncloned (parental) HONE-I and HONE-I clone (C)-40 cells were found to contain latent Epstein-Barr virus (EBV). Expression of the latent EBV genome in HONE-I C-40 cells has been examined. It was possible to detect a small percentage of cells spontaneously synthesizing EBV early antigen (EA) and virus capsid antigen (VCA) by immunofluorescence (IF). In addition, the EBV nuclear antigens (EBNA-I and EBNA-2), as well as the EBV latent membrane protein (LMP) were detected in the HONE-I cells. Attempts were made to induce the latent EBV genome in these cells with iododeoxyuridine (IUdR). We observed a significant increase in the number of EA/VCA-positive cells, an increase in EBV DNA, the synthesis of virus particles, and the rescue of infectious virus after treatment of HONE-I C-40 cells with IUdR. The HONE-I C-40 cells should facilitate studies of the expression and regulation of the EBV genome in NPC epithelial tumor cells, which have not previously been available.     

Segregation of the EBV-determined nuclear antigen (EBNA) in somatic cell hybrids derived from the fusion of a mouse fibroblast and a human Burkitt lymphoma line

Four independently derived hybrids between the mouse fibroblast line A9 and the human, Burkitt-lymphoma-derived lymphoblastoid cell line Daudi were studied for the presence of the Epstein-Barr virus (EBV) genome, the EBV-determined nuclear antigen (EBNA), other EBV-associated antigens, human surface immunoglobulin and the presence of human chromosomes. The four lines differed in the number of their EBV genomes. There was a parallelism between this number, as detected by c/RNA/DNA hybridization, and the frequency of EBNA-positive nuclei. None of the other EBV-antigens, EA, VCA or MA, was expressed at any time, either in the untreated hybrid cells or after IUDR-treatment. The hybrids did not carry detectable surface-associated immunoglobulin or EBV-receptors. The presence of the EBV genome was coincident with the maintenance of human chromosomes, but the hybrids that have lost detectable viral genomes and EBNA still contained a considerable number of human chromosomes, suggesting that the viral genome may be associated with a few chromosomes only.     

Differential inhibition of epstein-barr virus induction by the amino acid analogue,L-canavanine

The effect of an amino acid analogue, L-canavanine, on the synthesis of Epstein-Barr virus (EBV) antigens was investigated in lymphoblastoid cells. The analysis revealed that after infection of BJAB and NC-37 cells with P3HR-I EBV synthesis of early antigen (EA) was not affected by canavanine in concentrations up to 8.4 mM. The synthesis of EBV-determined nuclear antigen (EBNA) and of viral capsid antigen (VCA) was significantly inhibited at concentrations higher than 2.8 mM. Spontaneous induction of EA in P3HR-I cells was not affected by canavanine. On the other hand, EA induction by the tumor promoter TPA, by iododeoxyuridine (IdUrd), by antiserum to human IgM and by n-butyric acid was clearly inhibited by this treatment. Application of 0.3 mM canavanine resulted in more than 95% inhibition of EA induction by TPA. Under these conditions cell growth and incorporation of radiolabelled amino acids into an acid-insoluble fraction was significantly impaired. Differential treatment of the cells with canavanine established that EA induction was completely suppressed when the cells were treated concomitantly with canavanine and TPA. Subsequent treatment with canavanine after prior exposure to TPA resulted in some viral antigen induction depending on the time period of TPA exposure. Pretreatment of the cells overnight with canavanine followed by washing and addition of the tumor promoter did not suppress EA induction by TPA. These data support the concept that EA induction by superinfection follows a different pathway from antigen induction by chemical inducers.     

Epstein�CBarr virus antibody level and gastric cancer risk in Korea: a nested case�Ccontrol study

Background:

Few cohort studies have investigated Epstein–Barr virus (EBV) infection before the occurrence of gastric cancer.

Methods:

Among 14 440 cohort participants, 100 incident gastric cancer cases were individually matched to two controls. Epstein–Barr virus antibodies IgG and IgA against viral capsid antigen (VCA), EBV nuclear antigen (EBNA) antibody IgG, and early antigen (EA) antibody IgG were measured using enzyme immunoassays (EIAs).

Results:

The highest titres of VCA IgG (odds ratio (OR): 1.37, 95% confidence interval (CI): 0.62–3.06) or EBNA IgG (OR: 0.87, 95% CI: 0.51–1.46) were not associated with gastric cancer risk.

Conclusion:

Higher levels of VCA IgG or EBNA IgG were not associated with increased risk of gastric adenocarcinoma in Koreans.