The role of glycoprotein H in Varicella-zoster virus pathogenesis
Abstract/Contents
- Abstract
- Glycoprotein H (gH) plays an essential role in virus binding, entry and fusion of the Herpesviridae. Varicella-zoster virus (VZV) is an important human pathogen that causes varicella (chicken pox) and herpes zoster (shingles). VZV gH function has not be analyzed in depth. gH function was demonstrated to be important for VZV pathogenesis in skin xenografts in vivo by administration of anti-gH mAb 206, a conformation dependent neutralizing antibody. Antibody administration prevented infection in 42% of skin xenografts, and reduced virus replication and lesion formation in the remaining skin xenografts. Antibody binding to gH altered gH localization following endocytosis, preventing gH trafficking to the trans-Golgi network for virus secondary envelopment. Antibody binding to gH within the virus envelope resulted in internalization of virus particles, possibly for targeted degradation. Deletion of ORF 37, which encodes gH, demonstrated that gH was essential for VZV pathogenesis. Mutational analysis demonstrated that the N-terminus of the protein formed a structural epitope required for efficient VZV pathogenesis in vivo. Several neutralizing anti-gH antibodies target this epitope. A region of the C-terminus was required for VZV pathogenesis, and for efficient virus-induced cell-cell fusion. Predicted [alpha]-helices that might act as heptad repeats or fusion peptides were also required for gH function and VZV pathogenesis. Cysteine residues were important for gH maturation and transport, and possibly for correct expression of gH on the cell surface. Altogether, these studies demonstrate the importance of structural and functional domains for gH-dependent fusion and VZV pathogenesis.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Vleck, Susan Elizabeth |
|---|---|
| Associated with | Stanford University, Department of Microbiology and Immunology |
| Primary advisor | Arvin, Ann M |
| Thesis advisor | Arvin, Ann M |
| Thesis advisor | Glenn, Jeffrey S, 1962- |
| Thesis advisor | Greenberg, Harry B |
| Thesis advisor | Kirkegaard, Karla |
| Advisor | Glenn, Jeffrey S, 1962- |
| Advisor | Greenberg, Harry B |
| Advisor | Kirkegaard, Karla |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Susan Elizabeth Vleck. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis (Ph. D.)--Stanford University, 2010. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Susan Elizabeth Vleck
- License
- This work is licensed under a Creative Commons Attribution Non Commercial No Derivatives 3.0 Unported license (CC BY-NC-ND).
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