Date of Award

1-1-2018

Document Type

Masters Thesis

Degree Name

M.S.

Organizational Unit

Biological Sciences

First Advisor

Schuyler B. Van Engelenburg, Ph.D.

Second Advisor

Joseph Angleson

Third Advisor

Todd Blankenship

Fourth Advisor

John Latham

Keywords

HIV-1, HIV type 1, HIV, Env, Envelope glycoprotein, iPALM, Interferometric PALM, Superresolution, Virus assembly

Abstract

Human Immunodeficiency Virus type 1 (HIV-1) replicates by forcing infected host cells to produce new virus particles, which assemble form protein components on the inner leaflet of the host cell's plasma membrane. This involves incorporation of the essential viral envelope glycoprotein (Env) into a structural lattice of viral Gag proteins. The mechanism of Env recruitment and incorporation is not well understood. To better define this process, we seek to describe the timing of Env-Gag encounters during particle assembly by measuring angular positions of Env proteins about the surfaces of budding particles. Using three-dimensional superresolution microscopy, we show that Env distributions are biased toward the necks of budding particles, indicating incorporation of Env late in the assembly of the lattice. We show that this behavior is dependent on the host cell type and on the long cytoplasmic tail of Env. We propose a model wherein Env incorporation is regulated by opposing mechanisms: Gag lattice trapping of Env cytoplasmic tails, and intracellular sequestering of Env during lattice assembly.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Rights Holder

Carmen Anne Buttler

Provenance

Received from ProQuest

File Format

application/pdf

Language

en

File Size

91 p.

Discipline

Virology, Molecular biology, Cellular biology



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