| Título: | DNA SENSING ACTIVITY AND VIRAL INHIBITION OF HUMAN NUCLEAR DNA SENSORS |
| Autores: | Li, Tuo |
| Fecha: |
2013-09-16 2013-09-16 2013 |
| Publicador: | Universidad de Princenton |
| Fuente: |
 |
| Tipo: | Academic dissertations (Ph.D.) |
| Tema: |
DNA recognition Herpesvirus Immune evasion Posttranslational modifications Proteomics PYHIN proteins Immunology Molecular biology Virology |
| Descripción: | Human cells are protected by cell-intrinsic mechanisms that specifically detect microbial pathogens and elicit innate immune response. Such activities are essential in restricting viral infections. Despite the extensive knowledge about cytoplasmic sensing processes, little is understood about the nuclear counterpart. In this thesis, this poorly understood immune response to nuclear viral DNA is studied from two perspectives--host antiviral defense and viral immune evasion. In Chapter I, an overview to current understandings of cell-intrinsic immune response to foreign nucleic acids is first summarized. An important protein family, PYHIN proteins, is then introduced for their emerging roles in detecting intracellular viral DNA. Finally, I briefly describe a powerful technology, mass spectrometry-based proteomics, in studying host and pathogen interactions. In Chapter II, I describe experiments that mechanistically investigated the role of one PYHIN protein, the interferon inducible protein IFI16, in detecting nuclear viral DNA and eliciting interferon response. The results demonstrate IFI16 as the first known nuclear DNA sensor, and identify acetylation within its conserved nuclear localization signal as a novel molecular toggle that regulates the sensing ability of IFI16. In Chapter III, I show strong evidence that the major tegument protein pUL83 of human cytomegalovirus (HCMV) blocks IFI16-mediated nuclear DNA sensing. The results establish that the pUL83-IFI16 interaction critically determines the immunological outcome of HCMV infections in human cells, and showcase an intricate interplay between host and a viral pathogen. In Chapter IV, I explore the role of another PYHIN protein, IFIX, as a novel DNA sensor. Evidence is described to show that IFIX has a similar function with IFI16. In Chapter V, a new mass spectrometer, MALDI-LTQ-Orbitrap XL is functionally assessed for characterizing isolated protein complexes, a technique frequently utilized in the above chapters, highlighting useful applications of proteomics in studying host and virus interactions. |
| Idioma: | Inglés |
1 Engineering solutions for a carbon-constrained world por Celia, M. A.,Nordbotten, J. M. | 6 Impact of capillary forces on large-scale migration of CO2 por Nordbotten, Jan M.,Dahle, Helge K. |
2 Analysis of Plume Extent using Analytical Solutions for CO2 Storage por Nordbotten, Jan M.,Celia, Michael A. | 7 Impact of geological heterogeneity on early-stage CO2 plume migration por Ashraf, Meisam,Lie, Knut-Andreas,Nilsen, Halvor M.,Nordbotten, Jan M.,Skorstad, Arne |
3 A model-oriented benchmark problem for CO2 storage por Dahle, Helge K.,Eigestad, Geir T.,Nordbotten, Jan M.,Pruess, K. | 8 CO2 trapping in sloping aqiufers: High resolution numerical simulations por Elenius, Maria,Tchelepi, Hamdi,Johannsen, Klaus |
4 Report from CO2 storage workshop por Dahle, Helge K.,Lien, Martha,Nordbotten, Jan M.,Lie, Knut-Andreas,Braathen, Alvar,Helmig, Rainer,Class, Holger,Celia, Michael A. | 9 Streamline methods for parabolic differential equations por Hafver, Jørn |
5 Summary of Princeton Workshop on Geological Storage of CO2 por Celia, Michael A.,Nordbotten, Jan M.,Bachu, Stefan,Kavetski, Dmitri,Gasda, Sarah | 10 Vertically Averaged Models for CO2 Storage in Porous Media por Hammer, Andreas |