Mononucleosis in the laboratory.

(See the articles by Balfour et al. and Woodberry et al., on pages 1505–12 and 1513–24, respectively.) Figure 1. Epstein-Barr virus DNA in blood. Viral DNA in lymphocytes (top) may be present as either episomal DNA (left) or episomal and linear DNA packaged into capsids (right). Viral DNA in serum or plasma (bottom) may be present as either fragments of naked DNA resulting from apoptotic cell death or virions. Laboratory investigation of infectiousmono-nucleosis long preceded any knowledge of the etiologic virus [1]. The characteristic mononuclear leukocytosis associated with Pfeiffer glandular fever was reported in 1920. Heterophile antibodies were recognized 12 years later [2]. A specific viral link was established only after the ser-endipitous observation that a technician recovering from infectious mononucle-osis had seroconverted to Epstein-Barr virus (EBV) [3]. A series of studies shortly thereafter confirmed the association. In more recent years, a great deal of effort has focused on the viral genome, structure and function of the virion, and aspects of gene regulation, particularly lymphocyte-immortalizing and growth-transforming properties and association with various types of tumors—including Burkitt lymphoma, nasopharyngeal car-cinoma, posttransplantation lymphoma, Hodgkin lymphoma, AIDS lymphoma, nasal lymphoma, leiomyosarcoma in im-munocompromised patients, and gastric carcinoma [4]. In this issue of the Journal of Infectious Diseases, 2 investigations of the laboratory correlates of infectious mono-nucleosis are presented. One is focused on measurement of viral copy number [5], and the other is focused on the cellular immune response to viral antigens [6]. In considering the study by Balfour et al. [5] of viral copy number in association with infectious mononucleosis, it must be remembered that measurements of viral copy number may reflect the presence of latent or lytic infection or both (figure 1). Thus, latently infected B cells harbor double stranded viral episomes, and the measurement of viral copy number in blood may simply reflect the number of latent episomes in B cells. But B cells may also support lytic cycle replication, and viral copy number may therefore reflect virion production. In cell-free blood (serum or plasma), encapsidated viral genomes (vi-rions) may be detected. But viral DNA may be also be released without the protective virion capsid or envelope from latently infected cells, most notably tumor cells undergoing apoptosis. In patients with nasopharyngeal carci-noma, EBV DNA is detected in high copy numbers in serum or plasma but not in mononuclear cells [7–11]. Pretreatment viral copy number in cell-free blood is an important adverse …