KSHV-induced oncogenesis

Excerpt

Human infection by KSHV is associated with the development of at least three proliferative disorders: Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL) and a subset of multicentric Castleman’s disease (MCD). In keeping with the classification of KSHV as a lymphotropic (γ2) herpesvirus, two of these (PEL and MCD) are primary disorders of the B cell lineage. The third, KS, is a more complex lesion driven by proliferation of cells of endothelial lineage. KSHV is the second human γ-herpesvirus to be linked to neoplasia (EBV being the first). As such, many notions about how KSHV engenders these lesions have been heavily influenced by paradigms derived from the study of EBV-induced malignancies. In EBV, the viral latency program is powerfully immortalizing in vitro, and is thought to be the principal genetic program driving virus-related tumorigenesis. Lytic infection, while presumed important for dissemination of infection to target cells early in infection (and following lytic reactivation at later times), is not thought to play a direct role in the histogenesis of the tumors. As we shall see, although many parallels indeed exist with EBV, the distinctive features of the KSHV-associated diseases makes routine extrapolation from other viral models an enterprise to be undertaken with caution. In this chapter, we will review the biology of the KSHV-associated malignancies and consider the cellular and molecular mechanisms by which KSHV infection contributes to their pathogenesis.