Human Cytomegalovirus Modulation of Signal Transduction - Human Cytomegalovirus - page 199

Human Cytomegalovirus Modulation of Signal
Transduction

A. D. Yurochko

Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206

Signaling Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207

Receptor/Ligand-Mediated Signaling: Viral Glycoproteins . . . . . . . . . . . . . . . . . . . . . . . . 208

Captured Cellular Enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210

Tegument Protein-Mediated Signaling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211

Other Viral Gene Products That Modulate Signaling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212

Biological Rationale for Modulation of Host Cell Signaling . . . . . . . . . . . . . . . . . . . . . . . . . 212

Role of Signaling in Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215

Final Thoughts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216

Abstract An upregulation of cellular signaling pathways is observed in multiple
cell types upon human cytomegalovirus (HCMV) infection, suggesting that a global
feature of HCMV infection is the activation of the host cell. HCMV initiates and
maintains cellular signaling through a multitiered process that is dependent on a
series of events: (1) the viral glycoprotein ligand interacts with its cognate receptor,
(2) cellular enzymes and viral tegument proteins present in the incoming virion are
released and (3) a variety of viral gene products are expressed. Viral-mediated cel-
lular modification has differential outcomes depending on the cell type infected. In
permissive cell types, such as diploid fibroblasts, the upregulation of cellular signal-
ing pathways following infection can initiate the viral gene cascade and promote
the efficient transcription of multiple viral gene classes. In other cell types, such as
endothelial cells and monocytes/macrophages, the upregulation of cellular pathways
initiates functional host changes that allow viral spread to multiple organ systems.
Together, the modification of signaling processes appears to be part of a thematic

A. D. Yurochko
Department of Microbiology and Immunology, Center for Molecular and Tumor Virology,
Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center,
1501 Kings Highway Shreveport , LA 71130-3932 , USA
[e-mail]