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Hull Thesis Final2.67 MB
Embargoed Access, Embargo ends: 03/19/2027
Thesis
Herpes simplex virus 1 envelope glycoprotein C shields glycoprotein D to protect virions from entry-blocking antibodies
Washington State University
Master of Science (MS), Washington State University
12/2024
DOI:
https://doi.org/10.7273/000007188
Abstract
Like many other viruses, herpes simplex virus 1 (HSV-1) has acquired a range of immune evasive strategies that have aided in spread and persistence of the virus in human populations. During viral entry, HSV-1 glycoprotein D (gD) must interact with its cognate receptor, nectin-1, making gD essential for entry into host cells. Following nectin-1 binding, interaction between gD and the heterodimer glycoprotein H and L (gH/gL) is important to the fusion cascade. Neutralizing monoclonal antibodies (MAbs) against gD can either block receptor binding or interaction with gH/gL. Here we investigated the ability for another HSV-1 envelope protein, glycoprotein C (gC) to block anti-gD MAbs from binding and neutralizing HSV-1. When gC is deleted from the HSV-1 genome and is therefore not expressed (HSV-1 Δ gC), HSV-1 is 2- to 16-fold more sensitive to neutralization by anti-gD MAbs than the wild type rescuant virus (HSV-1 gCR). When probed under native conditions, gD on the HSV-1 ΔgC viral envelope was 2.7- to 5.6-fold more reactive with anti-gD MAbs. Receptor blocking anti-gD MAbs were more potent in their ability to block HSV-1 ΔgC from binding to nectin-1 compared to HSV-1 gCR. Additionally, nectin-1 was able to block entry of HSV-1 ΔgC into cells more robustly than HSV-1 gCR. Both HSV-1 ΔgC and gCR contain similar levels of surface glycoproteins and major capsid protein VP5, suggesting the lack of gC is responsible for any differences in antibody binding and receptor binding between the two viruses. Here, we posit that viral gC is broadly protecting both the receptor-binding and gH/gL binding domains of gD.
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Details
- Title
- Herpes simplex virus 1 envelope glycoprotein C shields glycoprotein D to protect virions from entry-blocking antibodies
- Creators
- McKenna A. Hull
- Contributors
- Viveka Vadyvaloo (Chair)Bronwyn Gunn (Committee Member)Dana Shaw (Committee Member)Michael Letko (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- College of Veterinary Medicine
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Number of pages
- 46
- Identifiers
- 99901195202001842
- Language
- English
- Resource Type
- Thesis