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Virokines in the Pathogenesis of Cancer: Focus on Human Herpesvirus 8
Author(s) -
KLOUCHE MARIAM,
CARRUBA GIUSEPPE,
CASTAGNETTA LUIGI,
ROSEJOHN STEFAN
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1322.038
Subject(s) - biology , autocrine signalling , primary effusion lymphoma , immune system , immunology , cancer research , paracrine signalling , signal transduction , cancer , virology , virus , microbiology and biotechnology , receptor , genetics
A bstract : During evolution, DNA viruses have captured a broad array of cellular genes involved in immune recognition and growth control that are nonessential for viral replication. The encoded virokines and viroceptors may act as mimetics or antagonists of their cellular homologues, altering signal transduction and cell communication towards survival of virus‐infected cells. Human herpesvirus type 8 (HHV8) is the most recently identified human oncogenic herpesvirus. It is associated with Kaposi's sarcoma and lymphoproliferative diseases, such as pleural effusion lymphomas and multicentric Castleman's disease. HHV8 has captured a unique number of cellular regulatory genes, which redirect gene expression and cell growth, prevent apoptosis and immune recognition, and interfere with tumor suppressor gene function. HHV8 encodes a unique virokine, viral interleukin‐6, which is particularly relevant for the pathogenesis of HHV8‐associated tumors, since it participates in transformation and mediates autocrine and paracrine mitogenic and proinflammatory effects. Viral IL‐6 differs fundamentally from human IL‐6 in receptor engagement for signal transduction and thus constitutes a singular model to understand the facets of human and viral cytokine biology. We provide an overview of the role of virokines in cancer, with a particular focus on the differences of human and viral IL‐6 in the pathophysiology of HHV8‐associated tumors.