Antigens for Epstein-Barr Virus (EBV) Antibody Tests

Background

Epstein–Barr virus (EBV), also called human herpesvirus 4 (HHV4), belongs to the Gammaherpesviridae, genus Lymphocryptovirus. EBV can be spread through saliva, blood and semen, and usually causes infectious mononucleosis (IM). Some cases also show that this virus associates with several types of cancer and have a higher risk of certain autoimmune diseases. EBV has the ability to infect a very wide range of age of people. In the United States, about half of all five-year-old children and about 90% of adults have evidence of previous infection. The major cell types infected by EBV are epithelial cells and B cells. Once EBV's initial lytic infection is brought under control, EBV latency persists in the individual's B cells for the rest of the individual's life.

Table 1. Epstein-Barr virus (EBV) proteins and their functions (Houen G and Trier NH. 2021)

EBV contains a double-strand DNA about 172 kilobase pairs which encoding approximately 85 proteins. Epstein–Barr virus infects host cell and hence proliferates in it would experience four stages: an Entry to the cell by using viral glycoprotein gp350, lytic replication, latency and reactivation. In latency, only a few viral genes are expressed, which includes the six EBV nuclear proteins: EBNA-1, EBNA-2, EBNA-3A, EBNA-3B, EBNA-3C, EBNA-LP, and three latent membrane proteins: LMP-1, LMP-2A, LMP-2B.

Fig. 1 EBV life cycle in healthy carriers (Smatti MK, et al. 2018)

EBV specific serological assays, such as ELISA, EIA, IFA, chemoluminescence, and immunoblot, are the simplest way to test for EBV infection and for evaluating acute versus remote infection in healthy individuals. Among the proteins encoded in the EBV genome, several have been used for detection of antibodies to EBV including EBNA1, EBNA2, VCAp23, VCAp18, early antigen. Commercial immunoassays for detecting IgG and IgM against EBV are needed to detect at least three EBV antibodies: VCA-IgG, VCA-IgM, and EBNA-1 IgG, which are routinely used in combination to distinguish an acute from a remote infection. The presence of VCA IgM and VCA IgG without EBNA-1 IgG indicates a current acute infection, and the presence of VCA IgG and EBNA1 IgG without VCA IgM typically indicate a remote infection.