Contribution of Epstein⁻Barr Virus Latent Proteins to the Pathogenesis of Classical Hodgkin Lymphoma

Abstract

Pathogenic viruses have evolved to manipulate the host cell utilising a variety of strategies including expression of viral proteins to hijack or mimic the activity of cellular functions. DNA tumour viruses often establish latent infection in which no new virions are produced, characterized by the expression of a restricted repertoire of so-called latent viral genes. These latent genes serve to remodel cellular functions to ensure survival of the virus within host cells, often for the lifetime of the infected individual. However, under certain circumstances, virus infection may contribute to transformation of the host cell; this event is not a usual outcome of infection. Here, we review how the Epstein⁻Barr virus (EBV), the prototypic oncogenic human virus, modulates host cell functions, with a focus on the role of the EBV latent genes in classical Hodgkin lymphoma.

Keywords: B cells; Epstein–Barr virus; Hodgkin lymphoma; latency.

Figure 1

Epstein–Barr virus latent proteins expressed in Hodgkin/Reed–Sternberg cells. Depicted is a Hodgkin/Reed–Sternberg cell with indicated functions of the viral EBNA1, LMP1 and LMP2A proteins.

Figure 2

EBNA1 is an emerging target for therapeutic intervention. Shown is an HRS cell expressing EBNA1. Possibilities to target EBNA1 therapeutically are indicated and include the use of small-molecule inhibitors of EBNA1, for example using drugs that block EBNA1 binding to DNA and EBNA1-specific fluorescent peptide probes which prevent EBNA1 dimerization [109,110,111], therapeutic EBV vaccines including MVA-EBNA1-LMP2 containing an EBNA1-LMP2 fusion protein [112], and adoptive T-cell therapies [113,114]. Other approaches include relieving Gar-mediated suppression of EBNA1 translation which can potentially boost EBNA1 recognition by T cells (e.g., PhenDC3) [115].