Host factors in dengue virus infection: Identification, characterization and their potential as therapeutic targets

Sudip Khadka, Purdue University

Abstract

Dengue virus (DENV), the causative agent of dengue fever, dengue hemorrhagic fever and dengue shock syndrome, infects over 230 million people worldwide every year. Due to limited coding capacity of its genome DENV relies on the host processes for completion of its life cycle. Often virus uses protein-protein interactions to subvert host systems. This dissertation summarizes findings from studies carried out to identify and understand the role of host factors in DENV infection. First, I describe the findings from a large scale yeast two-hybrid screen carried out to identify the human proteins that interact with DENV proteins. Results from this study show more than 100 human proteins were identified from the screen. Subsets of these proteins were found to associate with viral proteins in infected cells and were required for virus production and replication. I next describe the findings from study of interaction between the DENV NS5 protein and cellular DEAD-box helicases. This study allowed for mapping of the sites of interaction on the helicases and NS5 protein. Finally, I describe the findings that show cellular vATPase inhibitors inhibit DENV infection. Results from this study show that cellular processes can be targeted for antiviral activity. Taken together these results summarize identification, characterization and targeting of host factors for the study of potential antivirals.

Degree

Ph.D.

Advisors

LaCount, Purdue University.

Subject Area

Public health|Virology

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