Mechanisms of Adenovirus Membrane Permeabilization

<p>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.</p><p>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.</p><p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Microbiology and Immunology

Year dc:date.available

2011

Author dc:creator

• Maier, Oana

• Virology

Repository record dc:identifier

https://ecommons.luc.edu/luc_diss/283

OAI identifier oai:identifier

oai:ecommons.luc.edu:luc_diss-1282