Biophysical characterization of the entry mechanisms of enveloped viruses
Abstract/Contents
- Abstract
- Enveloped viruses are a diverse group of agents that pose a threat to global health and economic stability. An enveloped virus consists of a lipid bilayer surrounding the particle, surface glycoproteins involved in entry, and a viral genome necessary for replication. To infect a host, the virus must interact with a host membrane and undergo membrane fusion in order to release its genome for replication. Because of the conserved nature of this process, understanding virus entry at the molecular level is critical. While virus infection and entry have been extensively examined over many decades, the molecular mechanism(s) of entry and critical membrane components remain poorly characterized for many enveloped viruses due in part to the convolution of binding and membrane fusion in many cellular based assays, the requirement for receptor identification and reconstitution, and the extreme heterogeneity of the glycocalyx surrounding the cell membrane. Model membrane systems provide a platform to examine these complex mechanistic questions surrounding virus entry. This dissertation develops model membrane platforms using single particle measurements to examine mechanistic processes of virus entry for several enveloped viruses. The Boxer lab pioneered the development of DNA-lipids as membrane tethers and recently demonstrated that DNA-lipids can be used to bind influenza to a target membrane without altering lipid mixing kinetics. This dissertation expands this receptor-agnostic platform towards novel enveloped viruses which do not require a host receptor for fusion and explores the tunability of receptor agnostic platforms. Controlled complexity is introduced into a model membrane platform in the effort to reconstruct essential components of the glycocalyx to understand its role in Influenza entry. This dissertation seeks to examine the mechanism of virus entry with the least number of confounding variables while still reconstructing critical host components. These single virus measurements deconvolve viral binding and membrane fusion to identify previously obfuscated components in each process.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Webster, Elizabeth René |
|---|---|
| Degree supervisor | Boxer, Steven G. (Steven George), 1947- |
| Thesis advisor | Boxer, Steven G. (Steven George), 1947- |
| Thesis advisor | Cui, Bianxiao |
| Thesis advisor | Kim, Peter, 1958- |
| Degree committee member | Cui, Bianxiao |
| Degree committee member | Kim, Peter, 1958- |
| Associated with | Stanford University, Department of Chemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Elizabeth René Webster. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Elizabeth Rene Webster
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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