The cytomegalovirus homolog of interleukin-10 requires phosphatidylinositol 3-kinase activity for inhibition of cytokine synthesis in monocytes.
Human cytomegalovirus (CMV) has evolved numerous strategies for evading host immune defenses, including piracy of cellular cytokines. A viral homolog of interleukin-10, designated cmvIL-10, binds to the cellular IL-10 receptor and effects potent immune suppression. The signaling pathways employed by cmvIL-10 were investigated, and the classic IL-10R/JAK1/Stat3 pathway was found to be activated in monocytes. However, inhibition of JAK1 had little effect on cmvIL-10-mediated suppression of tumor necrosis factor alpha (TNF-alpha) production. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway had a more significant impact on TNF-alpha levels but did not completely relieve the immune suppression, demonstrating that cmvIL-10 stimulates multiple signaling pathways to modulate cell function.
Spencer
Juliet V
JV
Department of Biology, University of San Francisco, 2130 Fulton St., San Francisco, CA 94117, USA. jspencer@usfca.edu
D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D015536:Down-Regulation; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology* / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology / Q000821:virology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019869:Phosphatidylinositol 3-Kinases