Serological Diagnosis of EBV Infection

Definitive diagnosis of EBV infection is best done by serological or molecular biological tests. Infected B cells are stimulated to secrete immunoglobulins, producing among other antibodies; a so-called heterophile IgM antibody whose detection is one of the most widely used diagnostic tests for EBV infection. This heterophile antibody is not specific for EBV antigens but binds to antigens present on heterologous red blood cells (that is, those of other animals, such as sheep or goat) and agglutinates them.

In addition, specific antibody responses are generated against several EBV-specific antigens, and the appearance of different antibodies is informative as to the time of infection and the pattern of virus replication (see figure). The presence of IgM antibody against the EBV capsid antigen (VCA) indicates that the infection is acute; this antibody declines gradually in the convalescent phase. Because of the long incubation period of the virus, anti-VCA IgG antibody is also detectable at the onset of illness. The continued presence of EBV antigens in the host maintains antibody production throughout life.

Antibodies to so-called early antigens (EA) are produced mainly in the convalescent phase (1-6 months after disease onset); they then disappear. The absence of EA antibody indicates that the virus is mostly quiescent, and is not undergoing replication on large scale. If the infection is reactivated, EA antibody titers rise again. Antigens expressed later in the viral life cycle, during its latent phase, are the EBNA (Epstein-Barr nuclear antigens). Appearance of EBNA antibody indicates that the virus has been present in the body for at least few months.