Publication Date:
2002-11-16
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chatterjee, Malini -- Osborne, Julie -- Bestetti, Giovanna -- Chang, Yuan -- Moore, Patrick S -- CA76586/CA/NCI NIH HHS/ -- CA87661/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Nov 15;298(5597):1432-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12434062" target="_blank"〉PubMed〈/a〉
Keywords:
Antigens, CD/genetics/metabolism
;
Autocrine Communication
;
*Cell Division
;
Cytokine Receptor gp130
;
Down-Regulation
;
Feedback, Physiological
;
Genes, Viral
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Herpesvirus 8, Human/genetics/immunology/*physiology
;
Humans
;
Interferon-alpha/pharmacology/*physiology
;
Interleukin-6/genetics/*physiology
;
Membrane Glycoproteins/genetics/metabolism
;
Mutation
;
Promoter Regions, Genetic
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Receptors, Interleukin-6/genetics/metabolism
;
Signal Transduction
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Tetradecanoylphorbol Acetate/pharmacology
;
Transcription, Genetic
;
Tumor Cells, Cultured
;
Up-Regulation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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