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Authors: Javitt, Aaron
Advisors: Cristea, Ileana
Department: Molecular Biology
Class Year: 2015
Abstract: The antiviral factor interferon inducible protein 16 (IFI16) is a sensor of foreign DNA in the nucleus. A critical member of innate and intrinsic immunity processes, IFI16 binds herpesvirus DNA in the nucleus during infection. In response to DNA binding, IFI16 stimulates the production of interferon and cytokines through the STING-TBK1-IRF3 pathway. IFI16 has also been shown to have other critical roles during infection, serving as a suppressor of viral transcription. During Herpes Simplex Virus 1 (HSV-1) infection, these roles of IFI16 require it to be recruited to pre-replication sites in the nucleus where the viral genome is deposited. Despite all that is known about the function of IFI16 during infection, many of the cofactors responsible for binding HSV-1 genomes and mediating IFN upregulation through STING remain unknown. Using a combination of proteomics and virology - based methods, I characterized many of the interactions of IFI16 during HSV-1 infection. The newly identified interactions of IFI16 lend insight into the roles it plays in binding to and suppressing the replication of HSV-1 genomes. Through immunopurification and mass spectrometry analysis, IFI16 was found to interact with proteins from the sub-nuclear Nuclear Domain 10 (ND10). This complex has also been shown to associate with HSV-1 genomes and is recruited to pre-replication sites during infection, thereby playing a role in antiviral cellular defense. In addition, IFI16 was shown to associate with many HSV-1 proteins involved in HSV-1 genome transcription. I demonstrated that the ND10 component PML and the HIN200 domain of IFI16 are necessary for the recruitment of IFI16 to HSV-1 pre-replication sites. Finally, I examined the role of IFI16 and PML in IFN-induced apoptotic induction during HSV-1 infection.
Extent: 87 pages
Type of Material: Princeton University Senior Theses
Language: en_US
Appears in Collections:Molecular Biology, 1954-2020

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