Human herpesvirus 8-associated neoplasms: the roles of viral replication and antiviral treatment.

Abstract

In this review, we highlight the importance of human herpesvirus 8 (HHV-8) lytic replication and the potential for antiviral therapies to prevent or treat HHV-8-related neoplasms. Diseases caused by HHV-8 infection include Kaposi sarcoma, multicentric Castleman disease (MCD), and primary effusion lymphoma (PEL), which occur primarily in patients with HIV infection. Kaposi sarcoma is the most common AIDS-associated malignancy worldwide. MCD and PEL occur less commonly but, like Kaposi sarcoma, are associated with poor treatment outcomes. Like all herpesviruses, HHV-8 is capable of either latent or lytic infection of cells. Although HHV-8 infection of tumor cells is predominately latent, accumulating data point to the importance of both lytic phase viral gene products and production of infectious virus. Antiviral agents that target herpesvirus DNA synthesis, such as ganciclovir, inhibit HHV-8 lytic replication and can prevent Kaposi sarcoma. Several HIV protease inhibitors may interfere with tumor growth and angiogenesis, and one protease inhibitor, nelfinavir, directly inhibits HHV-8 replication in vitro. Controlled trials are indicated to determine the clinical utility of antiviral suppression of HHV-8 replication, and identify the optimal antiretroviral regimens, for the prevention and treatment of Kaposi sarcoma.