Microbial pathogens and their hosts have evolved complex adaptations to ensure their individual survival, resulting in a so-called "molecular arms race." While hosts may have acquired diverse mechanisms to protect themselves from the microbial invader, pathogens have developed elaborate strategies to evade and subvert these defenses. Viruses and hookworms are important pathogens which have evolved to successfully invade and infect their human hosts. Although structural biology has provided significant mechanistic insight into these processes of invasion, many specific host-pathogen interactions and their dynamics have not been well studied or characterized.
The work presented in this dissertation clarifies the mechanisms of cellular entry of one particular family of viruses, the flaviviruses, and discusses strategies for viral clearance by host cells. Additional insight into the role of a cytoplasmic DNA sensor, LRRFIP1, in mediating an innate immune response to non-flavivirus microbial infection is presented. Finally, strategies for the development of small-molecule or peptide inhibitors of virus entry and hookworm infection are proposed.
|School Location:||United States -- Connecticut|
|Source:||DAI-B 75/09(E), Dissertation Abstracts International|
|Subjects:||Biochemistry, Biophysics, Immunology|
|Keywords:||DNA sensors, Flavivirus, Host-pathogen interactions, Innate immune, Membrane fusion|
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