Background: Recently, we detected Kaposi's sarcoma-associated herpesvirus (KSHV), a novel member of the herpesvirus family, in the bone marrow dendritic cells of myeloma patients (Rettig et al. Science 276: 1851, 1997). These infected dendritic cells also expressed RNA transcripts of the viral interleukin-6 (IL-6) gene, the human homologue of which is a critical paracrine growth factor for myeloma. The viral genome also contains a homologue to macrophage inhibitory protein 1a(MIP-1a), viral MIP-1a, which is also transcribed in infected dendritic cells. Human MIP-1a, a chemokine produced by dendritic cells, serves as a chemoattractant for numerous cell types, including dendritic cells and B cells. Thus, we believe that viral MIP-1a functions in an autocrine fashion on infected dendritic cells, whereas viral IL-6 behaves as a paracrine growth factor for myeloma cells.

Hypothesis: KSHV plays an important role in the propagation of myeloma growth, and the expressed viral IL-6 and MIP-1a proteins within infected stromal cells of MM patients are crucial in this regard.

Specific Aims: 1. To study the potential growth-promoting effects of a rvIL-6 ex-pressing human bone marrow stromal cell line on myeloma cells; 2. To study the potential growth-promoting effects of a recombinant viral MIP-1a-expressing human bone marrow stromal cell line on myeloma cells.