Infectious mononucleosis: detection of herpeslike virus and reticular aggregates of small cytoplasmic particles in continuous lymphoid cell lines derived from peripheral blood.

Although an etiologic agent has not been isolated and identified, infectious mononucleosis has long been suspected to be an infectious disease, presumably of viral etiology. This concept is further supported by certain epidemiological features of the disease and by the nature of the acute illness. Recently, cytomegalovirus,' myxovirus,2 and the herpeslike virus (HLV)5 have all been implicated in the pathogenesis of this disease in man. In ultrastructural studies of circulating atypical lymphocytes from patients with infectious mononucleosis4 and of lymphoblastoid cells derived from bone marrow cultures of infectious mononucleosis patients,5 viral particles could not be demonstrated. Recent reports from several laboratories have revealed that circulating cells from the peripheral blood of patients with infectious mononucleosis have the potential for long-term proliferation in vitro.6 In this laboratory, 16 suspension cultures from nine patients with heterophile-positive infectious mononucleosis have been obtained in continuous culture. These established cell lines have been shown to synthesize immunoglobulin,7 to produce interferon,8 and to have chromosomal abnormalities similar to those consistently found in cultured cells derived from Burkitt's lymphoma.9 In the course of studying the fine structural features of these cell lines, viruslike particles have been detected and identified. In the present communication the results of these findings will be reported. Materials and Methods.-Sixteen continuous suspension cultures were established from nine patients with heterophile-positive infectious mononucleosis (Table 1) by means of techniques which have been described previously.6 Samples of cell suspensions were examined periodically for the presence of microbial agents.10 In each instance, cell lines were found to be free of detectable viruses, bacteria, fungi, mycoplasma, and endotoxins. From nine patients with infectious mononucleosis, 14 cultures were processed for electron microscopy (Table 2). As controls, other continuous cultures from peripheral blood were processed collaterally-one from a patient with lymphoblastic leukemia and another from a patient with leukocytosis of unknown etiology. In addition, thoracic duct and peripheral blood cultures from a patient with hyperglobulinemia of unknown etiology, buffy coats from the peripheral blood of six patients with infectious mononucleosis, and those from three clinically healthy individuals were also examined. Four of the contin-