The biology of EB virus

Abstract

The target cell most commonly infected by the ubiquitous EB virus is the B lymphocyte, and infection <i>in vitro</i> results in transformation and establishment of lymphoblastoid cell lines. Following transformation the EBV genome exists in both an integrated and an episomal form, and the number of genome equivalents per cell shows considerable variation. Transformed cells vary also in the level of expression of infectious virus, and may exhibit a number of EBV-related antigens detectable by immunofluorescence (IF), complement fixation, immunodiffusion or radioimmunoassay, The viral capsid antigen (VCA) is useful in routine diagnostic IF tests for antibody to EBV. The presence of an EBV-associated nuclear antigen (EBNA) correlates well with the detection in the cells of EBV genome bk molecular hybridization and EBNA is therefore a relatively simple indicator of the EBV-transformed state of cells. There is also a complex of membrane antigens (MA) on the surface of transformed cells. In addition to this transformation of normal B lymphocytes. EBV is able to superinfect lymphoid cell lines of B cell origin but are devoid of EBV genome. Finally, there is some evidence that certain epitheloid cell lines may possess EBV receptors. Three clinical entities have been so far associated with EBV; infectious mononucleosis (IM), Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPL). In IM, it is generally accepted that the atypical mononuclear cells represenr largely a response of T lymphocytes to EBV-infection of B lymphocytes. Antibodies to EBV usually appear by the time of onset and a rise in titre to VCA after onset is rarely detected. Transient IgM antibody to EBV occurs and provides a more specific serological test. In convalescence and thereafter. EBV-infected cells are found consistently only in lymph nodes, unless recrudescence occurs. The association of BL with EBV initially rested on the increased antibody response to EBV and received support by the detcction of the EBV genome in most BL of African origin although the non-African form may or may not carry the genome. A problem in the biology of EBV is the form of the virus during its long persistence following the primary infection. Our <i>in vitro</i> studies have alloued the development of an experimental system in which typical EBV transformation is completely inhibited. The inhibited lymphocytes are infected and carry the EBV genome, and the inhibition is reversible by simple adjustment of the culture conditions. Inhibition of EBV transformation is specifically mediated by a mononuclear cell population from the peripheral blood of persons with prior EBV infection. The importance of these findings is the demonstration that an immune process can modify EBV infection of lymphocytes without cell death, and prevent their subsequent proliferation as transformed cells.