Infection of rhesus monkeys and chimpanzees with Epstein-Barr virus.

Seventy-two nonhuman primates were entered into a long-term study to evaluate the pathogenicity of Epstein-Barr virus (EBV). Infectious virus was inoculated into 42 rhesus monkeys, 4 chimpanzees and 1 cynomolgus monkey. Immunostimulation or immunosuppression was attempted in 34 of these animals to enhance the oncogenic potential of the virus. Eleven inoculated animals were followed for more than 3 years and two were observed for 8 years. No tumors were observed in any of the animals; however, serological evaluation of the 47 inoculated primates and 25 matched controls indicated that at least 14 rhesus monkeys and the cynomolgus monkey were successfully infected with EBV. The potential use of rhesus monkeys as a model for EBV-induced disease in humans is discussed.

Antibody-dependent cell-mediated cytotoxicity against Epstein-Barr virus membrane antigen in African Burkitt's lymphoma.

Serial samples of sera from patients with African Burkitt's lymphoma were tested for antibody against Epstein-Barr virus (EBV)-specific membrane antigen (MA) by the antibody-dependent cell-mediated cytotoxicity assay (ADCC). Titers of patients in the long-term survivor group were generally higher than those found in the sera of patients in the short-term survivor group. Although ADCC titers to EBV-MA were not useful in predicting which patients would relapse there was a definite relationship between ADCC titer and prognosis. The individual differences in ADCC titers in patients in remission may explain the variability of responses that have been reported in studies on serotherapy with remission plasma.

Membrane antigen expression in Epstein-Barr virus-infected Raji cells in the presence of phosphonoacetic acid.

The expression of the Epstein-Barr virus (EBV)-induced membrane antigen (MA) in Raji cells experimentally infected with EBV concentrates was inhibited by phosphonoacetic acid (PAA) as determined by membrane immunofluorescence and inhibition of antibody-dependent lymphocyte cytotoxicity. PAA was only effective if present during the first 24 hr following virus adsorption, indicating that the synthesis of MA was primarily a late viral gene function requiring viral DNA synthesis.

Detection of Epstein-Barr virus antigens with enzyme-conjugated antibody.

Monospecific conjugated (fluorescein isothiocynate and horseradish peroxidase) goat antisera, prepared against three human immunoglobulin classes, IM (mu), IgG (gamma) and IgA (alpha), were compared for their ability to detect human Ig classes possessing specificity for Epstein-Barr virus (EBV) viral capsid antigens (VCA) in a chronically infected human lymphoid cell line, P3J-HRIK. It was determined that the enzyme system was significantly more sensitive than immunofluorescence in detecting most of the immunoglobulins in sera from cancer patients. Some patients with nasopharyngeal carcinomas (NPC) had extremely high levels of EBV-specific IgA, whereas cancers other than NPC may have lower EBV-specific IgA titers.

Comparative studies on immunity to EBV-associated antigens in NPC patients in North America, Tunisia, France and Hong Kong.

This study compared the relative antibody titers to EBV-related antigens in patients with nasopharyngeal carcinoma (NPC) and controls from a high-incidence (Hong Kong), an intermediate incidence (Tunisia), and two low-incidence (France, North America) areas to determine which of several EBV antibodies best differentiated NPC patients from controls. Antibodies measured include anti-virus capsid antigen (VCA), anti-early antigen (EA), anti-soluble antigen by complement-fixation (CF) and antibody-dependent lymphocyte cytotoxicity (ADLC). A matched pair analysis showed that significantly more NPC patients had higher VCA and EA but not CF or ADLC antibody titers than their matched cancer controls. The comparison of geometric mean titers between NPC cases and controls was more than seven-fold (816 vs 11.5) for EA antibody and more than three-fold (359.7 vs 95.4) for VCA anti-body (p less than 0.01). A two-fold difference was seen for CF antibody to soluble antigens (27.3 vs 12.9, p less than 0.01) and a three-fold difference (2657.7 vs 870.9, p less than 0.05) was observed for ADLC. Our finding of significant differences between NPC patients from four countries and their matched controls suggest that if EBV is the etiological agent of NPC in Chinese, it is quite likely to cause the majority of NPC cases in other ethnic groups living in other countries as well.

Soluble proteins of human bronchogenic carcinomas.

Solid-phase affinity chromatography has been used to search for tumor-associated proteins of bronchogenic carcinomas. All of the apparently normal proteins were removed from extracts of squamous cell carcinoma, large cell carcinoma, and adenocarcinoma of the lung. The remaining soluble proteins were partially characterized as to heat stability, approximate molecular size, electrophoretic mobility, and biologic function. These tumor-associated proteins were not tumor-specific by current definition. Neither lung cancer patients' lymphocytes nor serum proteins were specifically reactive with these tumor-associated proteins.