Herpesvirus saimiri (HVS) is the prototype gamma-2 herpesvirus, or rhadinovirus.  This is an increasingly important family of viruses due to the identification of the first human gamma-2 herpesvirus, Kasposi’s sarcoma-associated herpesvirus (KSHV).  KSHV has rapidly become the focus of intensive research as epidemiological studies suggest it is the etiologic agent of Kasposi’s sarcoma, the most common AIDs-related malignancy.  In addition, the presence of the virus has been detected in a variety of lymphoproliferative disorders including primary effusion lymphoma and multicentric Castleman’s disease.  At present analysis of KSHV lytic gene function is hampered by the lack of permissive cell culture system.  Therefore, the ability to easily grow and manipulate the prototype gamma-2 herpesvirus, HVS in vitro, has made this virus an attractive model to investigate the role of virus and cellular proteins in the regulation of the lytic temporal cascade of gamma-2 herpesviruses.

This review will describe the role of two major transcriptional control proteins encoded by gamma-2 herpesviruses.  There are encoded by the open reading frames (ORFs) 50 and 57.  The ORF 50 gene encodes two gene products, both of which activate transcription directly following interactions with promoters containing a specific sequence motif.  Deletion and gel retardation analysis have identified the consensus ORF 50 recognition sequence, CCN₉GG, required for ORF50 binding.  Once bound to the recognition sequence HVS ORF 50 recruits the TATA binding protein via a C-terminal transactivation domain.  This suggests that HVS ORF 50 recruits components of the TFIID complex allowing transcription initiation by RNA polymerase II.  In contrast, transactivation by the ORF 57 protein occurs independently of target gene promoter sequences and appears to be mediated at a post-transcriptional level.  Moreover, the ORF 57 protein has the ability to bind viral RNA, shuttle between the nucleus and cytoplasm and is required for efficient cytoplasmic accumulation of virus mRNA.  This suggests that ORF 57 is a nucleo-cytoplasmic shuttle protein which plays a pivotal role in mediating the nuclear export of viral transcripts.