Date of Award
2011
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Microbiology and Immunology
Abstract
For a successful infection to occur, a virus must first penetrate host cell membranes to access intracellular sites of viral replication. Currently the mechanism through which adenovirus, a non-enveloped, dsDNA virus, disrupts the endosomal membrane during cell entry is not well characterized.
Recent studies suggest that adenovirus protein VI, which is released from the interior of the capsid during cell entry, has all of the in vitro membrane lytic activity of the virion. We found that protein VI binds membranes via an amino-terminal 80 residue α-helical domain. Critical to this interaction are conserved hydrophobic and basic lysine residues within this domain. Membrane disruption can occur by two different mechanisms: transmembrane pore formation or membrane fragmentation. Our studies indicate that protein VI fragments membranes by inducing membrane curvature stress.
The observed mechanism for protein VI membrane disruption in vitro correlates with events during adenovirus endosomal escape. Recombinant viruses with mutations in protein VI α-helical domain that either decrease hydrophobicity or reverse the positive charge of lysine residues have a defect in endosomal escape. These data suggest that electrostatic and hydrophobic interactions between protein VI and the endosomal membrane are important for adenovirus endosomal escape.
Recommended Citation
Maier, Oana, "Mechanisms of Adenovirus Membrane Permeabilization" (2011). Dissertations. 283.
https://ecommons.luc.edu/luc_diss/283
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Copyright Statement
Copyright © 2011 Oana Maier
