Viral modulation of host factors for viral infectivity [electronic resource].

9781321063592

1 online resource (119 p.)

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The study of the interaction between a host and a viral antagonist is complex and essential for developing targeted therapeutic measures against these viruses. The host has many defensive mechanisms in place to prevent viral entry and prevent the virus from taking control of the cell. The virus, however, has specific counterattacks to many of these host defenses, including hijacking the host machinery to counteract the host immune response. A better understanding of the specific interactions between the host and virus may provide the basis for the development of improved therapeutics as well as expanding the depth of our knowledge about the basic biology of the host cell while under viral attack. Here, I present new, detailed insights into the mechanisms of two specific examples of host-virus interactions. First, I discuss the interactions of the host factor BST-2, which restricts HIV-1 virus particle release, and Vpu of HIV-1, which depletes BST-2 from the cell through hijacking of the host cellular machinery. Given the presence of species-specific interactions, I created and studied the solution behavior of numerous transmembrane constructs of both Vpu and BST-2. The roles of the clathrin adaptor protein complex 1 and adaptor protein complex 2 were each evaluated in BST-2 depletion from the cell surface by Vpu. I also investigated numerous novel BST-2/Vpu interactions. I detail my work to obtain structural insight into the transcriptional activator Zebra of Epstein Barr Virus and its non-canonical DNA binding mode that allows for specific recognition of viral promoters amongst the host DNA. I established a system for expression of Zebra protein that recapitulates the methylation dependent binding, which is crucial for viral conversion to the disease-causing state. I also have established that Zebra can bind to DNA duplexes of varying lengths which provides a starting point for obtaining structural information of the protein-DNA binding interaction. Together these studies provide insight into the complicated host-virus interactions that lead to disease and may aid in developing antiviral agents.

Books / Online / Dissertations & Theses

English

February 04, 2015

Thesis (Ph.D.)--Yale University, 2014.

Yale University.