Viruses lack self-propulsion. We have extended those studies by identifying and sequencing a third fragment of HHV-8 DNA encoding a viral thymidylate synthetase (TS) gene. The position of the R1 gene is equivalent to that of the saimiri transforming protein (STP) of herpesvirus saimiri (HVS) and of K1 of KSHV, other members of the gamma-2 or rhadinovirus subgroup of herpesviruses. In two highly divergent sequence variants of the right end of the KSHV genome, alternative splicing of eight exons located between KSHV ORF 75 and the terminal repeats yields transcripts appropriate for proteins with up to 12 transmembrane domains, followed by a hydrophilic C-terminal, presumably cytoplasmic, domain. The first rhadinovirus lineage consists of KSHV and its closely related homologs RFHVMn, RFHVMm, and ChRV-1, while the second more distantly related lineage consists of RRV, MneRV-2, and ChRV-2. Substitution mutations demonstrated that the lack of collagen repeats but not an SH2 binding motif contributed to the nontransforming phenotype of STP-B. We demonstrate that ORF 73 interacts with the cellular protein p32 and triggers the accumulation of p32 in the nucleus.
Using reporter gene-based transient-transfection assays, we demonstrate that ORF 73 can transactivate a number of heterologous promoter constructs and also upregulate its own promoter. (A) Phylogenetic tree depicting the three subfamilies of herpesviruses: alpha, beta, and gamma. Thus, the major IE region of the BHV-4 genome could encode a family of proteins sharing a zinc finger domain.