N-linked glycosylation is required for optimal function of Kaposi's sarcoma herpesvirus-encoded, but not cellular, interleukin 6

J Exp Med. 2004 Feb 16;199(4):503-14. doi: 10.1084/jem.20031205.


Kaposi's sarcoma-associated herpesvirus interleukin-6 (vIL-6) is a structural and functional homologue of the human cytokine IL-6 (hIL-6). hIL-6 and vIL-6 exhibit similar biological functions and both act via the gp130 receptor subunit to activate the Janus tyrosine kinase (JAK)1 and signal transducer and activator of transcription (STAT)1/3 pathway. Here we show that vIL-6 is N-linked glycosylated at N78 and N89 and demonstrate that N-linked glycosylation at site N89 of vIL-6 markedly enhances binding to gp130, signaling through the JAK1-STAT1/3 pathway and functions in a cytokine-dependent cell proliferation bioassay. Although hIL-6 is also N-glycosylated at N73 and multiply O-glycosylated, neither N-linked nor O-linked glycosylation is necessary for IL-6 receptor alpha-dependent binding to gp130 or signaling through JAK1-STAT1/3. As distinct from vIL-6, unglycosylated hIL-6 is as potent as glycosylated hIL-6 in stimulating B cell proliferation. These findings highlight distinct functional roles of N-linked glycosylation in viral and cellular IL-6.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • B-Lymphocytes / immunology
  • Cell Division / immunology
  • Cell Line
  • Cell Line, Tumor
  • Cloning, Molecular
  • Contactins
  • Escherichia coli / genetics
  • Glycosylation
  • Herpesvirus 8, Human / immunology*
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology*
  • Lymphocyte Activation / immunology
  • Neural Cell Adhesion Molecules / immunology
  • Peptide Fragments / chemistry
  • Plasmids
  • Recombinant Proteins / immunology


  • Contactins
  • Interleukin-6
  • Neural Cell Adhesion Molecules
  • Peptide Fragments
  • Recombinant Proteins