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Journal of Virology, November 2006, p. 10874-10878, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.00767-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Signal Transduction by Human Herpesvirus 8 Viral Interleukin-6 (vIL-6) Is Modulated by the Nonsignaling gp80 Subunit of the IL-6 Receptor Complex and Is Distinct from Signaling Induced by Human IL-6{triangledown}

Fang Hu and John Nicholas*

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231

Received 14 April 2006/ Accepted 18 August 2006

Human herpesvirus 8 (HHV-8) viral interleukin-6 (vIL-6) mediates signaling through the gp130 signal transducer but unlike human IL-6 (hIL-6) does not require the nonsignaling gp80 {alpha} subunit of the IL-6 receptor complex. By utilizing a gp80-refractory vIL-6 variant, vIL-6(R189L), we found that signal transduction, as measured by STAT1 and STAT3 activation and gp130 tyrosine phosphorylation in gp80+/gp130+ HEK293T cells, was modulated by gp80. Furthermore, the signaling and BAF-130 cell growth-promoting activities of vIL-6 and hIL-6 could be distinguished, and exogenous addition of soluble gp80 enhanced cell growth supported by vIL-6. Our findings demonstrate that gp80 can modulate vIL-6 activity and that vIL-6 and hIL-6 signaling are not directly equivalent.


* Corresponding author. Mailing address: SKCCC at Johns Hopkins, 1650 Orleans Street, Room 309, Baltimore, MD 21231. Phone: (410) 502-6801. Fax: (410) 502-6802. E-mail: nichojo{at}jhmi.edu.

{triangledown} Published ahead of print on 6 September 2006.


Journal of Virology, November 2006, p. 10874-10878, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.00767-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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