N-linked glycosylation required for optimal function of Kaposi's sarcoma
herpesvirus encoded IL6

Srinivas Viswanathan
Yale University

Kaposi's sarcoma-associated herpesvirus (KSHV) interleukin-6 (vIL-6) is a structural and functional homologue of the human cytokine IL-6 (hIL-6). Like hIL-6, vIL-6 acts via the gp130 receptor subunit to activate the JAK1 and STAT 1/3 pathway. Viral IL-6 contains two N-glycosylation consensus sites at Asparagine 78 and Asparagine 89. Here, we show the importance of an N-linked glycosylation on Asparagine 89 of vIL-6 for binding to gp130, signalling through the JAK1-STAT1/3 pathway, and function in a cytokine-dependent cell proliferation bioassay. Although human IL-6 is also N-glycosylated (at Asparagine 73), its N-glycosylation is not necessary for binding gp130/IL6-Ra, signalling through JAK1/STAT1-3, or function in the proliferation bioassay. These findings highlight distinct functional roles of N-linked glycosylation in hIL-6 and vIL-6, and may provide some insight into the role of vIL-6 in KSHV pathogenesis.