Kaposi's sarcoma-associated herpesvirus: the role of lytic replication in targeted therapy.

Abstract

To discuss the role of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication in viral-associated diseases and assess the progress on targeting KSHV lytic replication as a strategy to prevent KSHV-related malignancies. New inhibitors of viral lytic replication are being developed as well as novel modalities are being investigated to target cellular processes that the virus hijacks during its life cycle. Research has also focused on reactivating viral lytic replication in latently infected tumour cells (lytic induction therapy) to promote death of tumour cells. KSHV is linked to three malignancies: Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman disease. Despite significant progress in understanding KSHV pathobiology, no therapeutic guidelines for the management of KSHV-related diseases exist, and current treatments are suboptimal and associated with toxicity. Antiherpesvirus drugs have shown inconsistent results in KSHV-associated malignancies that harbour the virus in a latent state. However, lytic replication plays a crucial role in the process of tumorigenesis. Therefore, not only antiviral agents directed against the virus replicative cycle but also agents that target cellular processes that are activated by the virus are being investigated. Antivirals may also be used in combination with inducers of the viral lytic stage.