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 (vIL-6) that shares 25% amino-acid identity with its human homologue. Human IL-6 is known to be a growth and differentiation factor of lymphatic cells and plays a potential role in the pathophysiology of various lymphoproliferative diseases. vIL-6 is expressed in HHV8-associated-diseases including Kaposi's sarcoma, Body-cavity-based-lymphoma and Castleman's disease, suggesting a pathogenetic involvement in the malignant growth of B-cell associated diseases and other malignant tumours. We expressed vIL-6 in Escherichia coli as a fusion protein with recombinant periplasmic maltose binding protein. After cleavage from the maltose binding protein moiety and purification, vIL-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 receptor (IL-6-R) suggesting that, in contrast to human IL-6, vIL-6 stimulated gp130 directly. Accordingly, vIL-6 activity could be inhibited by a soluble gp130 Fc Fusion protein. vIL-6 was shown to induce neuronal differentiation of rat pheochromocytoma cells and to stimulate colony formation of human hematopoietic progenitor cells. Thus, vIL-6 exhibits biologic activity that has only been observed for the IL-6/soluble IL-6-R complex but not for IL-6 alone. These properties are important for the evaluation of the pathophysiological potential of vIL-6.
Hoischen
S H
SH
Johannes Gutenberg University of Mainz, Germany.
Vollmer
P
P
März
P
P
Ozbek
S
S
Götze
K S
KS
Peschel
C
C
Jostock
T
T
Geib
T
T
Müllberg
J
J
Mechtersheimer
S
S
Fischer
M
M
Grötzinger
J
J
Galle
P R
PR
Rose-John
S
S
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D050822:Cytokine Receptor gp130; D019922:GAP-43 Protein / Q000187:drug effects / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D019288:Herpesvirus 8, Human; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells / Q000187:drug effects; D051381:Rats; D018123:Receptors, Interleukin / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*
D015703:Antigens, CD; D019922:GAP-43 Protein; C494199:IL6ST protein, human; C494201:Il6st protein, rat; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014764:Viral Proteins; C104543:interleukin 6-interleukin 6 receptor fusion protein, recombinant; D050822:Cytokine Receptor gp130