ABSTRACT
There is a strong scientific and commercial focus on developing vaccines and immunotherapeutic strategies for the treatment of Epstein-Barr virus (EBV)-associated diseases. This increased interest is due to a deeper understanding of the immune variables that control EBV infection and an appreciation of the biology of this potentially oncogenic virus [1,2]. Epstein-Barr virus, discovered in 1964 by Epstein and colleagues, is a human gamma herpesvirus that infects over 90% of the world’s population. It is a double-stranded DNA virus encoding approximately 100 proteins [3]. Primary infection most commonly occurs during childhood and is generally asymptomatic, resulting in a lifelong viral latency in B cells. In developed countries, primary infection is sometimes delayed until adolescence and then results in clinical infectious mononucleosis (IM) (commonly called as “glandular fever”). This clinical manifestation occurs in about 50% of adolescents experiencing primary EBV infection (typically following kissing) and is characterized by fatigue, pharyngitis, fever, cervical lymphadenopathy, and splenomegaly. The major target of EBV infection is apparently the B lymphocyte, although a role for squamous epithelial cells cannot be unequivocally discounted. During primary infection (Figure 1), colonization of the lymphoid system occurs through virus-driven expansion of infected B cells that selectively express six latent EBV nuclear antigens (EBNAs 14, 6, -LP) and latent membrane proteins (LMPs 1, 2A, and 2B) [4,5]. These latently infected B cells maintain a lifelong virus carrier state and constitute the reservoir on which viral persistence depends. Viral shedding into the oropharynx is another feature of primary EBV infection and arises from expression of the “lytic switch” protein BZLF1 [6], which launches the productive cycle cascade. Lytic and structural proteins gp85, BMLF1, BMRF1, BHRF1, and gp350 are also a feature of virus replication [7].
