Epstein–Barr Virus: Molecular Biology

Epstein–Barr virus (EBV) is a potent transformer of B lymphocytes in vitro and is associated with a half dozen human cancers. Yet, while 90% of the world population is persistently infected with this herpesvirus, the overall incidence of EBV-related malignancy is exceedingly low. This reflects the highly evolved and finely balanced relationship between EBV and its host. Viral persistence is mediated through a small subset of the more than 80 genes encoded by EBV, the majority of which contribute to virus replication and are silent during latent infection. The latency-associated proteins are a six-member family of EBV nuclear proteins (EBNAs), three integral membrane proteins (LMPs), and several small proteins potentially expressed from a family of alternatively spliced RNAs ( BARTs). In addition, two small noncoding RNAs ( EBERs) and multiple micro-RNAs are expressed during latency. Known functions of the latency-associated gene products range from viral genome maintenance, regulation of EBV and cellular gene transcription, promotion of cell survival and proliferation, to evasion of host immune-response mechanisms. Selective expression of the EBV latency genes within several distinct latency programs promotes the establishment and maintenance of a persistent infection, while ensuring that the oncogenic potential of the virus is limited.