Independence of herpesvirus-induced T cell lymphoma from viral cyclin D homologue

Cyclin D family members are cellular protooncogenes, and their viral homolo gues in the Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesviru s type 8 [HHV-8]) and the closely related Herpesvirus saimiri have been imp licated as putative cofactors of viral transformation and pathogenesis. KSH V is regularly found in Kaposi's sarcoma and in the primary effusion B cell lymphoma and Castleman's disease associated with Immunosuppression and AID S. H. saimiri strain C488 transforms human and marmoset T cells in vitro an d causes polyclonal T cell lymphoma in New World monkeys. The viral cyclins stimulate cell cycle progression of quiescent fibroblasts, and they form a ctive cyclin-dependent kinase (CDK)6 complexes of broad substrate specifici ty that can resist and downregulate cellular CDK inhibitors. This study sho ws that the viral cyclin of H. saimiri strain C488 is not required for vira l replication, T cell transformation, and pathogenicity in New World primat es.