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.
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.
Hu
Fang
F
SKCCC at Johns Hopkins, 1650 Orleans Street, Room 309, Baltimore, MD 21231, USA.
Nicholas
John
J
D002460:Cell Line; D050822:Cytokine Receptor gp130 / Q000502:physiology; D014644:Genetic Variation; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D021122:Protein Subunits; D019947:Receptors, Interleukin-6 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D015850:Interleukin-6; D021122:Protein Subunits; D019947:Receptors, Interleukin-6; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014764:Viral Proteins; C113250:interleukin-6 receptor alpha; D050822:Cytokine Receptor gp130