Contribution of Epstein–Barr Virus Lytic Proteins to Cancer Hallmarks and Implications from Other Oncoviruses

SIMPLE SUMMARY: Epstein–Barr virus (EBV) is a gamma-herpesvirus associated with a broad variety of cancers. It employs two modes of viral replication, i.e., latent and lytic cycles in which both can contribute to oncogenesis. Increasing evidence supports the contribution of the lytic cycle in cancer development while only a limited number of lytic proteins have been characterized in detail. This review aims to summarize the currently known tumorigenic properties of the lytic proteins based on their contribution to the hallmarks of cancer and to postulate the roles of some partially characterized or uncharacterized lytic proteins based on their homologs in other herpesviruses and oncoviruses. ABSTRACT: Epstein–Barr virus (EBV) is a prevalent human gamma-herpesvirus that infects the majority of the adult population worldwide and is associated with several lymphoid and epithelial malignancies. EBV displays a biphasic life cycle, namely, latent and lytic replication cycles, expressing a diversity of viral proteins. Among the EBV proteins being expressed during both latent and lytic cycles, the oncogenic roles of EBV lytic proteins are largely uncharacterized. In this review, the established contributions of EBV lytic proteins in tumorigenesis are summarized according to the cancer hallmarks displayed. We further postulate the oncogenic properties of several EBV lytic proteins by comparing the evolutionary conserved oncogenic mechanisms in other herpesviruses and oncoviruses.