Persistent γ-herpesvirus Infections : What Can We Learn from an Experimental Mouse Model?

The human γ-herpesviruses, EBV (or HHV-4) and Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) are oncogenic viruses that induce a readily controlled lytic infection followed by the establishment of life-long latency. This quiescent state is maintained by the host immune system. In most cases the persistent infection is asymptomatic or accompanied by benign cellular proliferations. However, occasionally persistent γ-herpesvirus infection is associated with the development of malignancies, including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, Kaposi's sarcoma, and B cell lymphoproliferative syndromes. Most of these malignancies develop after years of viral dormancy, and are associated with viral reactivation. The important role for immune control in preventing the development of malignancies is illustrated by the fact that immunosuppression, as a consequence of disease (AIDS) or posttransplant immunosuppressive therapy, leads to the development of EBV-associated lymphoproliferative syndromes and lymphomas, and KSHV-associated Kaposi's sarcoma (1, 2). Because...