Date of Award

Spring 2013

Document Type

Thesis

Degree Name

Bachelor of Science

Department

Biochemistry & Molecular Biol.

Abstract

After receptor mediated endocytosis into an endosome, human Adenovirus Type 5 (Ad5) undergoes structural changes that allow the virus to release a viral protein, pVI, that lyses the endosome and releases the virus core into the cytosol, where it travels to the nucleus to insert its genome. Structural studies of Ad5 at a range of pHs typical of endosomes (7.5-4.5) using a transmission electron microscope show that Ad5 undergoes asymmetrical loss of proteins from vertex regions at the pH of the late endosome (pH5.15). Following further acidification, Ad5 ejects core material preferentially through one vertex—indicating an asymmetry at one vertex of the capsid. Further studies done using SDS-PAGE show that as pH is decreased, the virus capsid releases pVI and pVII, and later pV from the virus capsid. This correlates with an increase in infectivity of pH6.2 virus and a decrease in infectivity of the virus at pH 5.2 and 4.6; indicating that at those two pH values, essential proteins were lost from the capsid. We propose a revision of the process of Ad5 disassembly as the virus enters the cell via acidifying endosomes.

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