Regan N. Theiler 1996-2003
Resident, Obstetrics & Gynecology
Emory University School of Medicine, Atlanta, GA
De Paul University 1996
Medical Microbiology & Immunology PhD 2001
Theresa Compton
Membrane topology and complex formation of human cytomegalovirus glycoprotein O
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This dissertation presents structural studies of the Human Cytomegalovirus (HCMV) tripartite glycoprotein complex comprised of glycoproteins H, L, and O (gH, gL, and gO). Glycoproteins H and L are found throughout the herpesviruses, mediating fusion of the viral envelope with host cell membranes during viral entry. Glycoprotein O, however, is unique to the beta herpesvirus subfamily and has been characterized only in cytomegalovirus. Studies presented here explore the membrane topology of glycoprotein O, as well as structural determinants of gH/gL/gO complex formation. Experiments in chapter 2 demonstrate that gO, while not a transmembrane protein, shows membrane association in CMV-infected cells, but not in cells transfected with a gO expression plasmid. Chapters 3 and 4 describe reconstitution of the 240 kDa gH/gL/gO complex in two recombinant systems, and map a domain on the C-terminus of gH that is necessary for gH/gL/gO complex formation. Finally, chapter 5 details the discovery of novel virion-associated gO complexes, including gO/gL heterodimers, that arise at late stages of assembly. Together, these studies have changed our model of the gH/gL/gO complex to one of gH/gL/gO complexes, and have provided structural insight regarding multiple interactions of these three proteins. |
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| Thesis Publications |
- Theiler RN, Compton T. Distinct glycoprotein O complexes arise in a post-golgi compartment of cytomegalovirus-infected cells. J Virol 76:2890-2898, 2002
- Kinzler ER, Theiler RN, Compton T. Expression and reconstitution of the gH/gL/gO complex of human cytomegalovirus. J Clin Virol 25:S87-S95, 2002.
- Theiler RN, Compton T. Characterization of the signal peptide processing and membrane association of human cytomegalovirus glycoprotein O. J Biol Chem 276:39226-39231, 2001.
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