Epstein-Barr virus (EBV) is associated with a diverse range of tumors of both lymphoid and epithelial origin. Similar to other herpesviruses, EBV displays a bipartite life cycle consisting of latent and lytic phases. Current dogma indicates that the latent genes are key drivers in the pathogenesis of EBV-associated cancers, while the lytic genes are primarily responsible for viral transmission. In recent years, evidence has emerged to show that the EBV lytic phase also plays an important role in EBV tumorigenesis, and the expression of EBV lytic genes is frequently detected in tumor tissues and cell lines. The advent of next generation sequencing has allowed the comprehensive profiling of EBV gene expression, and this has revealed the consistent expression of several lytic genes across various types of EBV-associated cancers. In this review, we provide an overview of the functional implications of EBV lytic gene expression to the oncogenic process and discuss possible avenues for future investigations.
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