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Science 298 (5597): 1432-1435

Copyright © 2002 by the American Association for the Advancement of Science

Viral IL-6-Induced Cell Proliferation and Immune Evasion of Interferon Activity

Malini Chatterjee,1 Julie Osborne,1 Giovanna Bestetti,1 Yuan Chang,2* Patrick S. Moore2*

Lymphoma cells infected with Kaposi's sarcoma-associated herpesvirus are autocrine dependent on virus-derived interleukin-6 (IL-6), but not on cellular IL-6. During viral infection, host cells induce the antiviral factor interferon (IFN) to up-regulate p21, initiate cell cycle arrest, and inhibit virus replication. Viral IL-6, however, blocks IFN signaling. A viral transcriptional program exists in which only the viral IL-6 gene is directly activated by IFN-alpha , allowing the virus to modify its cellular environment by sensing and responding to levels of intracellular IFN signaling. The human cytokine cannot mimic this effect because IFN-alpha down-regulates the IL-6 receptor, gp80. Viral IL-6 bypasses the gp80 regulatory checkpoint by binding directly to the gp130 transducer molecule, resulting in tumor cell autocrine dependence on the viral cytokine for proliferation and survival.

1 Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
2 Molecular Virology Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA.
*   To whom correspondence should be addressed at Molecular Virology Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center 1.8, 5117 Centre Avenue, Pittsburgh, PA 15213, USA. E-mail: yc70{at}pitt.edu (Y.C.) and psm9{at}pitt.edu (P.S.M.)



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