Human herpes virus 8 interleukin-6 homologue triggers gp130 on neuronal and hematopoietic cells

Human herpes virus-8 (HHV8) encodes a cytokine named viral interleukin-6 (v IL-6) that shares 25% amino-acid identity with its human homologue. Human I L-6 is known to be a growth and differentiation factor of lymphatic cells a nd plays a potential role in the pathophysiology of various lymphoprolifera tive diseases. vIL-6 is expressed in HHV8-associated-diseases including Kap osi's sarcoma, Body-cavity-based-lymphoma and Castleman's disease, suggesti ng a pathogenetic involvement in the malignant growth of B-cell associated diseases and other malignant tumours. We expressed vIL-6 in Escherichia col i as a fusion protein with recombinant periplasmic maltose binding protein. After cleavage from the maltose binding protein moiety and purification, v IL-6 was shown to be correctly folded using circular dichroism spectroscopy . A rabbit antiserum was raised against the recombinant vIL-6 protein. vIL- 6 turned out to be active on cells that expressed gp130 but no IL-6 recepto r (IL-6-R) suggesting that, in contrast to human IL-6, vIL-6 stimulated gp1 30 directly. Accordingly, vIL-6 activity could be inhibited by a soluble gp 130 Fc Fusion protein. vIL-6 was shown to induce neuronal differentiation o f rat pheochromocytoma cells and to stimulate colony formation of human hem atopoietic progenitor cells. Thus, vIL-6 exhibits biologic activity that ha s only been observed for the IL-6/soluble IL-6-R complex but not for IL-6 a lone. These properties are important for the evaluation of the pathophysiol ogical potential of vIL-6.