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

2002; American Association for the Advancement of Science; Volume: 298; Issue: 5597 Linguagem: Inglês

10.1126/science.1074883

1095-9203

Malini Chatterjee, Julie Osborne, Giovanna Bestetti, Yuan Chang, Patrick S. Moore,

Cytomegalovirus and herpesvirus research

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.