HUMAN HERPESVIRUS-8 ENCODES A HOMOLOG OF INTERLEUKIN-6

Kaposi's sarcoma is a multifocal lesion that is reported to be greatly influenced by cytokines such as interleukin-6 (IL-6) and oncostatin M . DNA sequences of a novel human gammaherpesvirus, termed human herpes virus 8 (HHV-8) or Kaposi sarcoma-associated herpesvirus, have been id entified in all epidemiological forms of Kaposi's sarcoma with high fr equency. The presence of HHV-8 DNA is also clearly associated with cer tain B-cell lymphomas (body cavity-based lymphomas) and multicentric C astleman's disease. Sequence analysis of a 17-kb fragment revealed tha t adjacent to a block of conserved herpesvirus genes (major DNA-bindin g protein, glycoprotein B, and DNA polymerase), the genome of HHV-8 en codes structural homolog of IL-6. This cytokine is involved not only i n the pathogenesis of Kaposi's sarcoma but also in certain B-cell lymp homas and multicentric Castleman's disease. The viral counterpart of I L-6 (vIL-6) has conserved important features such as cysteine residues involved in disulfide bridging or an amino-terminal signal peptide. M ost notably, the region known to be involved in receptor binding is hi ghly conserved in vIL-6 This conservation of essential features and th e remarkable overlap between diseases associated with HHV-8 and diseas es associated with IL-6 disregulation clearly suggest that vIL-6 is in volved in HHV-8 pathogenesis.