KAPOSIS SARCOMA-ASSOCIATED HUMAN HERPESVIRUS-8 ENCODES HOMOLOGS OF MACROPHAGE INFLAMMATORY PROTEIN-1 AND INTERLEUKIN-6

Human herpesvirus-8 (HHV-8) has been detected in Kaposi's sarcoma (KS) lesions of all types (AIDS-related, classical and endemic), in body-c avity-based B-cell lymphomas (BCBLs) and in lesions of multicentric Ca stleman's disease (MCD). We have identified a major gamma-herpesvirus- divergent locus (DL-B) in HHV-8 DNA encoding several HHV-8 unique open reading frames (ORFs), including a homologue of interleukin-6 (IL-6) and two homologues of macrophage inflammatory protein MIP-1. We show t hat the HHV-8-encoded IL-6 homologue (vIL-6) shares functional propert ies with endogenous IL-6 proteins and that both vIL-6 and vMIP-1 trans cripts are present at high levels following butyrate induction of an H HV-8(+) BCBL cell line. Low amounts of constitutive vIL-6, but not vMI P-1, mRNA were also detected. The presence of a functional IL-6 homolo gue encoded by HHV-8 may provide a mechanistic model for the hypothesi zed role of HHV-8 in KS, MCD and BCBL that involves the mitogenic effe cts of vIL-6 on surrounding cells. MIP-1 proteins may enhance these ef fects through the chemotactic recruitment of endogenous cytokine-produ cing cells into affected tissues and could potentially influence HIV d isease progression in coinfected individuals through interactions with the HIV co-receptor CCR-5.