Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus linked to the development of Kaposi's sarcoma and a rare B cell lymphoma, primary effusion lymphoma. The KSHV gene ORF K9 encodes vIRF which is a protein with low but significant homology to members of the interferon (IFN) regulatory factor (IRF) family responsible for regulating intracellular interferon signal transduction (Moore PS, Boshoff C, Weiss RA and Chang Y. (1996). Science, 274, 1739-1744). vIRF inhibits IFN-beta signal transduction as measured using an IFN-responsive ISG54 reporter construct co-transfected with ORF K9 into HeLa and 293 cells. vIRF also suppresses genes under IFN regulatory control as shown by inhibition of the IFN-beta inducibility of p21WAF1/CIP1, however, no direct DNA-binding or protein-protein interactions characteristic for IRF repressor proteins were identified. Stable transfectant NIH3T3 clones expressing vIRF grew in soft agar and at low serum concentrations, lost contact inhibition and formed tumors after injection into nude mice indicating that vIRF has the properties of a viral oncogene. Since vIRF is primarily expressed in KSHV-infected B cells, not KS spindle cells, this study suggests that vIRF is a transforming oncogene active in B cell neoplasias that may provide a unique immune escape mechanism for infected cells. This data is consistent with tumor suppressor pathways serving a dual function as host cell antiviral pathways.

undersigned authors wish to report the following. ''Despite repeated attempts, we have been unable to repeat the PRF-mediated transcriptional activation of the cMYC promoter by these viral oncoproteins as described in this paper. In contrast, our findings that vIRF (1-3) and EBNA2 (4) interact with p300 and CBP have been shown independently by others. We can no longer support our conclusion of specific viral oncoprotein activation of the cMYC promoter through the PRF element. We regret the confusion that this may have caused

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We characterized the glycoprotein K (gK)-null herpes simplex virus type 1 [HSV-1] (KOS) ⌬gK and compared it to the gK-null virus HSV-1 F-gK␤ (L. Hutchinson et al., J. Virol. 69:5401-5413, 1995). ⌬gK and F-gK␤ mutant viruses produced small plaques on Vero cell monolayers at 48 h postinfection. F-gK␤ caused extensive fusion of 143TK cells that was sensitive to melittin, a specific inhibitor of gK-induced cell fusion, while ⌬gK virus did not fuse 143TK cells. A recombinant plasmid containing the truncated gK gene specified by F-gK␤ failed to rescue the ICP27-null virus KOS (d27-1), while a plasmid with the ⌬gK deletion rescued the d27-1 virus efficiently. ⌬gK virus yield was approximately 100,000-fold lower in stationary cells than in actively replicating Vero cells. The plaquing efficiencies of ⌬gK and F-gK␤ virus stocks on VK302 cells were similar, while the plaquing efficiency of F-gK␤ virus stocks on Vero cells was reduced nearly 10,000-fold in comparison to that of ⌬gK virus. Mutant ⌬gK and F-gK␤ infectious virions accumulated within Vero and HEp-2 cells but failed to translocate to extracellular spaces. ⌬gK capsids accumulated in the nuclei of Vero but not HEp-2 cells. Enveloped ⌬gK virions were visualized in the cytoplasms of both Vero and HEp-2 cells, and viral capsids were found in the cytoplasm of HEp-2 cells within vesicles. Glycoproteins B, C, D, and H were expressed on the surface of ⌬gK-infected Vero cells in amounts similar to those for KOS-infected Vero cells.These results indicate that gK is involved in nucleocapsid envelopment, and more importantly in the translocation of infectious virions from the cytoplasm to the extracellular spaces, and that actively replicating cells can partially compensate for the envelopment but not for the cellular egress deficiency of the ⌬gK virus.