Nonlytic spread of a naked virus

Placeholder Show Content

Abstract/Contents

Abstract
How do viruses spread from cell to cell? Enveloped viruses acquire their surrounding membranes by budding either through the plasma membrane or an internal membrane of infected cells. Thus, a newly budded enveloped virus finds itself either in the extracellular milieu or in a lumenal compartment from which it can exit the cell by conventional secretion. On the other hand, naked viruses such as poliovirus lack an external membrane. They are simply protein-nucleic acid complexes within the cytoplasm or nucleus of the infected cell, and thus would seem to have no other exit route than cell lysis. Poliovirus is a lytic virus, although a few examples of apparently nonlytic spread have been documented. Real demonstration of nonlytic spread for poliovirus or any other cytoplasmic constituent requires demonstration that a small amount of lysis in the cellular population is not responsible for the release of cytosolic material. The work in this thesis has demonstrated, for the first time, definitive nonlytic cell-to-cell spread of poliovirus. We have also shown a link between this type of spread and components of a conserved pathway called autophagy. Chapter 1 contains a review of the cell biology of poliovirus infection that has led to the hypothesis for nonlytic spread. In Chapter 2, we describe the time-lapse microscopy setup used to monitor real time cell-to-cell spread of poliovirus and some of the unique early observations of how the virus spreads. In Chapter 3, we dive into the role the autophagy pathway or its components play on the spread of poliovirus. Chapter 4 moves to the mouse model of poliomyelitis where we investigate how perturbing the autophagy pathway affects the pathogenesis of poliovirus. In Chapter 5, we demonstrate nonlytic spread of poliovirus in tissue culture and begin to dissect the mechanism for this type of spread. Finally, in Chapter 6, we draw conclusions about the possible role of nonlytic spread in the life cycle of poliovirus and why studying the role of autophagy in acute viral infections may be important.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2015
Issuance monographic
Language English

Creators/Contributors

Associated with Bird, Sara Whitney
Associated with Stanford University, Department of Microbiology and Immunology.
Primary advisor Kirkegaard, Karla
Thesis advisor Kirkegaard, Karla
Thesis advisor Covert, Markus
Thesis advisor Monack, Denise M
Thesis advisor Sonnenburg, Justin, 1973-
Advisor Covert, Markus
Advisor Monack, Denise M
Advisor Sonnenburg, Justin, 1973-

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Sara Whitney Bird.
Note Submitted to the Department of Microbiology and Immunology.
Thesis Thesis (Ph.D.)--Stanford University, 2015.
Location electronic resource

Access conditions

Copyright
© 2015 by Sara Whitney Bird
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

Also listed in

Loading usage metrics...