The kaposin B protein of KSHV activates the p38/MK2 pathway and stabilizes cytokine mRNAs.
Cytokine production plays a critical role in diseases caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Here we show that a latent KSHV gene product, kaposin B, increases the expression of cytokines by blocking the degradation of their messenger RNAs (mRNAs). Cytokine transcripts are normally unstable because they contain AU-rich elements (AREs) in their 3' noncoding regions that target them for degradation. Kaposin B reverses this instability by binding to and activating the kinase MK2, a target of the p38 mitogen-activated protein kinase signaling pathway and a known inhibitor of ARE-mRNA decay. These findings define an important mechanism linking latent KSHV infection to cytokine production, and also illustrate a distinctive mode by which viruses can selectively modulate mRNA turnover.
McCormick
Craig
C
Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Medicine, University of California, San Francisco, CA 94143, USA.
Ganem
Don
D
D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000378:metabolism*; D017735:Virus Latency; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000099190:MAP-Kinase-Activated Kinase 2
D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D014764:Viral Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C120136:kaposin B protein, Human herpesvirus 8