Introduction
The human gammaherpesviruses Epstein–Barr Virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are associated with a variety of malignancies involving cells of various lineages.
After primary infection and initial viral propagation in epithelial and lymphoid cells, both viruses establish latency in a subset of CD 19 positive B-cells. In this often lifelong asymptomatic stage, in which EBV genomes are detectable primarily in resting memory B-cells, the number of infected cells is extremely low and virus load is tightly controlled by the host cellular and humoral immune response.
Loss of this balance leads to an increase in viral load, which often precedes the onset of malignant diseases. Both tissue involvement and histopathology are highly variable between EBV - and KSHV -associated malignancies and involve either lymphoid (Burkitt's lymphoma and primary effusion lymphoma), epithelial (nasopharyngeal carcinoma), or endothelial (Kaposi's sarcoma) tissues.
However, common to all gammaherpesvirus-associated tumors is that the majority of tumor cells are latently infected, and harbor extrachromosomal circularized viral genomes called episomes that are replicated and segregated by the host cellular replication machinery indefinitely. This ability to maintain long-term latent infection in quiescent and proliferating cells may be a defining property shared by both the lymphocryptoviruses (LCV, represented by EBV) and the rhadinoviruses (RDV, represented by KSHV).
This chapter aims to summarize our current understanding of the underlying mechanisms by which EBV and KSHV achieve long-term episomal maintenance in latently infected cells, which conceptually can be viewed as a two step process: replication of the viral genome and faithful segregation to daughter cells (Fig. 24.1).