EBV: immunobiology and host response

Excerpt

The biology and immunology of Epstein–Barr virus (EBV) has continued to fascinate researchers because the lessons learnt provide a platform for understanding the interplay between the biology of this ubiquitous infection, the immune system seeking to restrict its spread and the emergence of a variety of malignancies. As with other gamma herpes viruses, EBV encodes a large set of lytic cycle genes together with a number of latent genes which are associated with expansion of the latent EBV pool in B-lymphocytes. Current evidence suggests that the virus gains entry into the body by infection of B-lymphocytes in the oral cavity via an interaction between the major viral glycoprotein gp340 and the complement receptor CR2 which is expressed on B-cells, although a role for CR2-expressing or non-expressing epithelial and/or T-cells cannot be totally discounted. In either case, evidence suggests that the earliest detectable event following primary infection is the expression of lytic cycle proteins resulting in the release of infectious virus into the oral cavity followed by a generalized seeding of latently infected B-lymphocytes throughout the body. This primary infection results in symptoms of acute infectious mononucleosis (IM) in about 50% of adolescents and is coincident with a marked lymphocytosis (dominated by EBV-specific cytotoxic T-cells) and the appearance of an IgM response to a variety of EBV proteins, most notably the viral capsid antigen, VCA. Current evidence suggests that this cytotoxic T-cell (CTL) response, which includes both CD4+ and CD8+ cells restricts expansion of these latently infected B-cells and results in a long-term carrier state in which there is an equilibrium between the level of secretion of the virus and the number of latently infected B-cells.