T-Cell Transformation and Oncogenesis by γ2-Herpesviruses

Abstract

gamma2-Herpesviruses, also termed rhadinoviruses, have long been known as animal pathogens causing lymphoproliferative diseases such as malignant catarrhal fever in cattle or T-cell lymphoma in certain Neotropical primates. The rhadinovirus prototype is Herpesvirus saimiri (HVS), a T-lymphotropic agent of squirrel monkeys (Saimiri sciureus); Herpesvirus ateles (HVA) is closely related to HVS. The first human rhadinovirus, human herpesvirus type 8 (HHV-8), was discovered a decade ago in Kaposi's sarcoma (KS) biopsies. It was found to be strongly associated with all forms of KS, as well as with multicentric Castleman's disease and primary effusion lymphoma (PEL). Since DNA of this virus is regularly found in all KS forms, and specifically in the spindle cells of KS, it was also termed KS-associated herpesvirus (KSHV). Several simian rhadinoviruses related to KSHV have been discovered in various Old World primates, though they seem only loosely associated with pathogenicity or tumor induction. In contrast, HVS and HVA cause T-cell lymphoma in numerous non-natural primate hosts; HVS strains of the subgroup C are capable of transforming human and simian T-lymphocytes to continuous growth in cell culture and can provide useful tools for T-cell immunology or gene transfer. Here, we describe their natural history, genome structure, biology, and pathogenesis in T-cell transformation and oncogenesis.