Dissertation
Conformational Changes in HSV gC and Fusion Activity of HSV Glycoproteins from a Hyperfusogenic Virus
Washington State University
Doctor of Philosophy (PhD), Washington State University
2023
DOI:
https://doi.org/10.7273/000006290
Abstract
Herpes simplex virus 1 (HSV-1) affects 60 to 90 percent of the world population. There is currently no vaccine available for HSV, and the only treatment for active infections is antivirals. Once infected with HSV, there is a lifelong latent infection with the possibility of reactivation caused by stress or in patients that are immunocompromised. Viral entry during infection is a target for vaccine development, so understanding the mechanisms of viral entry are important. For HSV entry to occur, viral glycoproteins B, D, H, and L are required. HSV glycoprotein C (gC) is important for low pH entry where it optimizes the function of the main fusogen glycoprotein B. Here we determined that mildly acidic pH triggered reversible conformational change in gC itself. A monoclonal antibody that binds to a linear sequence that includes residues within gC amino acids 33 to 123 inhibited low pH entry of HSV. This suggests that the gC N-terminus is particularly important. We also examined the fusion-from-without strain ANG strain of HSV-1 that has unique entry and fusion phenotypes. Sequencing revealed several mutations in HSV-1 ANG gB, gC, gD, gH, and gL genes. ANG gB, when expressed with wild type gD and gH/gL, increased membrane fusion, suggesting that ANG gB has hyperfusogenic cell-cell fusion activity. Replacing the wild type gD, gH, or gL with the corresponding ANG alleles did not enhance cell-cell fusion. Overall, we have increased our understanding of herpesviral membrane fusion and revealed novel potential viral determinants.
Metrics
6 File views/ downloads
29 Record Views
Details
- Title
- Conformational Changes in HSV gC and Fusion Activity of HSV Glycoproteins from a Hyperfusogenic Virus
- Creators
- Katrina Gianopulos
- Contributors
- Anthony V Nicola (Advisor)Alan G Goodman (Committee Member)Heather Koehler (Committee Member)Joshua Ramsay (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- School of Molecular Biosciences
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 77
- Identifiers
- 99901086432901842
- Language
- English
- Resource Type
- Dissertation