The role of MKK1/2 kinase activity in human cytomegalovirus infection

• Published in: Journal of general virology 2001-03, Vol.82 (3), p.493-497
• Main Authors: Johnson, Robert A, Ma, Xiu-Li, Yurochko, Andrew D, Huang, Eng-Shang
• Format: Article
• Language: English
• Subjects: Butadienes - pharmacology; Cells, Cultured; Cytomegalovirus - genetics; Cytomegalovirus - metabolism; Cytomegalovirus - physiology; DNA Replication - drug effects; DNA, Viral - biosynthesis; Enzyme Activation; Enzyme Inhibitors - pharmacology; extracellular signal-regulated kinase 1; extracellular signal-regulated kinase 2; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - enzymology; Fibroblasts - virology; Human cytomegalovirus; Humans; MAP Kinase Kinase 1; MAP Kinase Kinase 2; mitogen-activated protein kinase 1; Mitogen-Activated Protein Kinase 1 - metabolism; mitogen-activated protein kinase 2; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinase Kinases - metabolism; Mitogen-Activated Protein Kinase Kinases - physiology; Mitogen-Activated Protein Kinases - metabolism; Nitriles - pharmacology; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; Protein-Serine-Threonine Kinases - physiology; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Protein-Tyrosine Kinases - physiology; U0126; Viral Proteins - metabolism
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-82-3-493

Department of Microbiology and Immunology 1 , 32026 Lineberger Comprehensive Cancer Center, CB# 7295 2 , Department of Medicine 3 and Curriculum of Genetics and Molecular Biology 4 , University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA Author for correspondence: Eng-Shang Huang (at Lineberger Comprehensive Cancer Center). Fax [phone]. e-mail eshuang{at}med.unc.edu Human cytomegalovirus infection of quiescent fibroblasts was found to induce a bi-phasic activation of mitogen-activated protein kinase (MAPK) kinase 1 and 2 (MKK1/2) and two of their downstream targets, extracellular signal regulated kinase 1 and 2 (ERK1/2), as determined by Western blot analysis using phospho-specific antibodies. Treatment of infected fibroblasts with U0126, a potent and specific inhibitor of MKK1/2 kinase activity, completely blocked ERK1/2 activation following HCMV infection without affecting cell viability. Anti-viral studies demonstrate that in the presence of U0126, viral titres are reduced and viral DNA replication is inhibited. In addition, protein levels of two viral early genes that are required for viral DNA replication, UL44 and UL84, are significantly decreased in the presence of U0126. These results suggest that HCMV-mediated activation of MKK1/2 kinase activity enhances virus infectivity by ensuring timely initiation of viral DNA replication, possibly by regulating early gene expression.