K Hennessy

Expression of Epstein–Barr Virus Transformation–Associated Genes in Tissues of Patients with EBV Lymphoproliferative Disease

Epstein-Barr virus (EBV) has been associated with serious or fatal lymphoproliferative disease in immunocompromised patients. EBV nuclear protein 2 and latent membrane protein are characteristically expressed in B lymphocytes proliferating in vitro in response to growth transformation by EBV. These two proteins are thought to be effectors of lymphocyte growth since they increase the expression of B-lymphocyte activation (CD23) and cell-adhesion (LFA 3 and ICAM 1) molecules in vitro. Using monoclonal antibody-immune microscopy, we have demonstrated that these two EBV proteins and their associated B-lymphocyte activation or adhesion molecules are expressed in the infiltrating B lymphocytes in immunocompromised patients with EBV lymphoproliferative disease. These monoclonal antibodies should be useful in the early diagnosis of EBV lymphoproliferative disease and in distinguishing it from other B-lymphocyte cancers associated with EBV, such as Burkitts lymphoma. The finding of EBV nuclear protein 2 and latent membrane protein and their associated activation or adhesion molecules provides a further pathophysiologic link between EBV and the proliferation of B lymphocytes in immunocompromised patients.

Epstein-Barr virus (EBV) antigen-specific leukocyte migration inhibition (LMI) in infectious mononucleosis (IM): I. Kinetics and response to a membrane protein on EBV-transformed cells

Cell-mediated immune response of mononucleosis (IM) patients to Epstein-Barr virus (EBV)-determined antigens was measured by the leukocyte migration inhibition (LMI) assay. Patients in the acute phase of the disease failed to respond to partially purified nuclear antigen, EBNA, or to cell extracts that contained EBNA as the predominant EBV antigen. They showed a strong specific response to cell extracts enriched in early antigen (EA) and virus capsid antigen (VCA). The LMI response to EBNA appeared in convalescence in parallel with EBNA-specific antibodies, slightly later in children than in adults. Membrane fractions of EBV-carrying, virus nonproducer Raji cells induced an EBV-specific LMI at approximately the same time. A bacterial fusion protein containing the hydrophilic part of the virus-coded membrane antigen of latently EBV-infected cells also induced an EBV-specific response that parallelled the LMI reaction elicited by the Raji membrane fraction. This is in line with our previous finding (D. Sulitzeanu et al., J. Virol. 58, 230, 1986) that this fusion protein shares an epitope with Raji cell membranes.

Persistence and Expression of the Epstein-Barr Virus Genome in Latent Infection and Growth Transformation of Lymphocytes

Epstein-Barr Virus (EBV) is believed to be an important etiologic agent of nasopharyngeal cancers (NPC) especially of the anaplastic type since (i) NPC cells invariably harbor EBV (Wolf et al., 1975; Huang et al., 1974; Klein et al., 1974); (ii) EBV is believed to be a cause of human B lymphocyte tumors (Epstein and Achong, 1978); (iii) the immune response to EBV infection is predictive of NPC development and of prognosis (Henle et al., 1970; Zeng et al., 1980; Pearson et al., 1984); and (iv) most NPC tumors originate from an unique anatomic site where there is closest proximity between lymphoid cells in which EBV is latent and epithelial cells in which tumor originates (Prasad 1981). Because of difficulties in infecting epithelial cells with EBV and in propagating NPC cells in vitro, current knowledge of EBV-induced cell proliferation comes mostly from the human B-lymphocyte tumor model. Not only is EBV almost always present in burkitt lymphoma cells (Nonoyama et al., 1973; Lindahl et al., 1974); nut also, virus infection of lymphocytes in vitro leads to cell proliferation (Henle et al., 1976; Pope et al., 1968), virus-infected cells from tumors in nonhuman primates (Miller et al., 1977), and virus-transformed cells of varying stages of oncogenic potential can be grown in continuous culture (Nilsson 1971).