The human herpesvirus 8 (HHV-8) genome contains four tandemly arranged genes encoding viral interferon regulatory factors (vIRF-1 to 4) located between genes 57 and 58. Transcript mapping techniques were employed to determine the sizes, ends and splicing patterns of mRNAs specified by these genes in HHV-8-infected cell lines untreated or chemically induced into the lytic growth cycle. Depending on the cell line used, vIRF-3 transcription was minimally or not induced (i.e. expressed with latent kinetics), whereas the other vIRFs were inducible (i.e. expressed with lytic kinetics). Each gene possessed its own promoter (or promoters) and polyadenylation sites, and all but vIRF-1 were spliced from two exons. vIRF-1 was transcribed in uninduced and induced cells from a single initiation site preceded by a TATA box, with the possible use of an additional TATA box and initiation site in uninduced cells. In induced cells, vIRF-2 was transcribed from a single major initiation site preceded by a TATA box, and vIRF-4 was expressed from two sites each preceded by a TATA box. Transcripts for these genes were insufficiently abundant in uninduced cells to map the 5′-ends. vIRF-3 lacks an obvious TATA box and exhibited heterogeneous 5′-ends in uninduced and induced cells. These data clarify and extend our understanding of the structure and transcription of the HHV-8 vIRF genes.
This work was supported by the Medical Research Council, by a grant to D. J. B. and A. J. D. from the Association for International Cancer Research (ref. 01-242), and by grants to D. J. B. from the Cunningham Trust (ref. ACC/KM CT), the Wellcome Trust (ref. 059008/Z/99/Z) and the Royal Society (ref. 574006.G503/21709/SM). We thank Professor T. Schulz (University of Liverpool) for provision of the HBL-6, BCP-1 and Raji cell lines, Dr R. Ambinder (Johns Hopkins Medical School) for the JSC-1 cell line and Dr A. Moses (Oregon Health Sciences University) for tDMVECs. We are grateful to Professor D. McGeoch for helpful comments on the manuscript. We warmly acknowledge Dr F. Neipel (University of Erlangen-Nürnberg) for a discussion in 1999 on splicing of the vIRFs.