Antibody Responses to Two Epstein-Barr Virus Nuclear Antigens Defined by Gene Transfer

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Abstract
By transfecting small fragments of Epstein-Barr virus (EBV) DNA into cells, we defined two nuclear antigens, termed M and K, and examined serum from 258 subjects for antibodies against these antigens. We hoped to learn whether such single-antigen systems would clarify the association of EBV with various diseases. Although reactivity to M antigen was found in only 14 per cent of healthy EBV-seropositive subjects, 90 per cent of Chinese and North African patients with nasopharyngeal carcinoma had antibody to M. Nearly all persons (96 per cent) who were EBV seropositive, as judged by their serologic reaction to a nuclear antigen encoded by the complete virus (EBNA), had a reaction to K antigen. However, serum samples from three patients with chronic active EBV infection did not react to K, even though the serum contained anti-M titers above 1:1000. Lymphoid cells from one such patient carried a normal gene for K and made K protein of correct size. Therefore, in this patient the absence of antibody to K had not resulted from a viral mutation that destroyed the K protein. These serologic studies show that some patients with chronic active EBV infection have an abnormal immune response to a specific viral gene product. (N Engl J Med 1985; 312:750–5.)